RESUMEN
BACKGROUND: The aim was to investigate the association between colonic ischaemia and intra-abdominal pressure (IAP) after surgery for ruptured abdominal aortic aneurysm (rAAA). METHODS: Sigmoid colon perfusion was monitored with an intramucosal pH (pHi) tonometer. Patients with a pHi of 7.1 or less were treated for suspected hypovolaemia with intravenous colloids and colonoscopy. IAP was measured every 4 h. Patients with an IAP of 20 mmHg or more had neuromuscular blockade, relaparotomy or both. RESULTS: A total of 52 consecutive patients had open rAAA repair; 30-day mortality was 27 per cent. Eight patients died shortly after surgery. Fifteen were not monitored for practical reasons; mortality in this group was 33 per cent. IAP and pHi were measured throughout the stay in intensive care in the remaining 29 patients. Monitoring led to volume resuscitation in 25 patients, neuromuscular blockade in 16, colonoscopy in 19 and relaparotomy in two. One patient died in this group. Twenty-three of 29 patients had a pHi of 7.1 or less, of whom 15 had a pHi of 6.9 or less. Sixteen had an IAP of 20 mmHg or more, of whom ten also had a pHi below 6.90. Peak IAP values correlated with the simultaneously measured pHi (r = -0.39, P = 0.003). CONCLUSION: Raised IAP is an important mechanism behind colonic hypoperfusion after rAAA repair. Monitoring IAP and timely intervention may improve outcome.
Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Rotura de la Aorta/cirugía , Colitis Isquémica/etiología , Colon Sigmoide/irrigación sanguínea , Hipertensión/etiología , Complicaciones Posoperatorias/etiología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Colitis Isquémica/mortalidad , Femenino , Humanos , Hipertensión/mortalidad , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: In a previous investigation concerning the hemodynamic and metabolic changes over time displayed by sequential positron emission tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be identified (reduction of metabolic rate of oxygen [CMRO(2)] to approximately 60% of the contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an instrument for chemical brain monitoring, the aim of this subsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO(2) above or below the metabolic threshold) and the occurrence of reperfusion, as assessed by PET. METHODS: Continuous MD (2 probes in each brain) and sequential PET measurements were performed during MCA occlusion (2 hours) and 18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe regions were divided into 3 categories on the basis of whether CMRO(2) was below or above 60% of the contralateral region (metabolic threshold level) during MCA occlusion and whether reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). RESULTS: The lactate/pyruvate ratio, hypoxanthine, and glutamate showed similar patterns. MD probe regions with severe ischemia and reperfusion and probe regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never decreased to baseline. Penumbra MD probe regions displayed only slight transient increases during MCA occlusion and returned to baseline. CONCLUSIONS: This experimental study of focal ischemia showed that the extracellular changes of energy-related metabolites and glutamate differed depending on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.
Asunto(s)
Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/fisiopatología , Microdiálisis/métodos , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Tomografía Computarizada de Emisión/métodos , Animales , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , Circulación Cerebrovascular , Ácido Glutámico/metabolismo , Hipoxantina/metabolismo , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Ácido Láctico/metabolismo , Macaca mulatta , Consumo de Oxígeno , Ácido Pirúvico/metabolismo , Daño por Reperfusión/diagnóstico por imagenRESUMEN
Intracerebral microdialysis (MD) was applied in patients with subarachnoid hemorrhage. The regional CBF, the CMRO2, and oxygen extraction ratio (OER) were measured with simultaneous positron emission tomography (PET). The aim was to directly correlate alterations in dialysate levels of energy-related metabolites (lactate, lactate/pyruvate ratio, hypoxanthine) and excitatory amino acids (EAAs) (glutamate and aspartate) to the energy state in the MD probe region as determined by PET. Regional ischemia was defined according to Heiss et al. and Lassen (Heiss et al., 1992; Lassen, 1966). Whole-brain ischemia was considered present when the OER for the whole brain exceeded the mean whole-brain OER + 2 SD of six reference patients. In general, the presence of whole-brain ischemia and/or regional ischemia within the region of the MD probe was associated with increased levels of energy-related metabolites and EAAs retrieved by MD. Increased levels of energy-related metabolites and EAAs were only occasionally seen when PET did not show any signs of ischemia or when signs of regional ischemia were found remote from the MD probe region. Thus, the energy-related metabolites and EAAs may be used as extracellular "markers" of ischemia. PET may be of use in defining critical ischemic regions (tissue at risk) where the MD probe can be inserted for chemical monitoring.
Asunto(s)
Isquemia Encefálica/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Hemorragia Subaracnoidea/metabolismo , Tomografía Computarizada de Emisión , Anciano , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular , Metabolismo Energético , Aminoácidos Excitadores/metabolismo , Femenino , Humanos , Masculino , Microdiálisis , Persona de Mediana Edad , Consumo de Oxígeno , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/fisiopatologíaRESUMEN
Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N-methyl-D-aspartate receptor complexes. A significant and dose-dependent reduction of binding was measured as a result of displacement of (S)-[N-methyl-11C]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.
Asunto(s)
Encéfalo/metabolismo , Ketamina/administración & dosificación , Ketamina/farmacología , Tomografía Computarizada de Emisión , Adulto , Afecto/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Ketamina/sangre , Ketamina/farmacocinética , Masculino , Memoria/efectos de los fármacos , Persona de Mediana Edad , Dolor/prevención & control , Valores de Referencia , Distribución TisularRESUMEN
The effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and L-tyrosine infusion on [11C]dopamine synthesis was analyzed in the striatum of Rhesus using positron emission tomography (PET). The rate for decarboxylation from L-[beta-11C]DOPA to [11C]dopamine was calculated using a graphical method with cerebellum as a reference region. Although the peripheral administration of 6R-BH4 at low dose (2 mg/kg) did not provide a significant increase in the rate of dopamine biosynthesis, a high dose of 6R-BH4 (20 mg/kg) induced an elevation of the rate. This 6R-BH4-induced elevation of the dopamine synthesis rate was further dose-dependently enhanced by the continuous infusion of L-tyrosine (0.2 and 1.0 mumol/min/kg). L-Tyrosine infusion with a rate of 1.0 mumol/min/kg caused an enhancement of the rate even during low dose administration of 6R-BH4 (2 mg/kg). L-Tyrosine infusion alone did not induce any elevation of the dopamine biosynthesis rate. The analysis of plasma indicated that the metabolic ratios of L-[beta-11C]DOPA to each metabolite were not affected by 6R-BH4 and/or L-tyrosine infusion. The results suggest that the low dose loading of tyrosine facilitates the activity of 6R-BH4 on the presynaptic dopamine biosynthesis, and also that the combined effects can be monitored by PET using L-[beta-11C]DOPA as a biochemical probe.
Asunto(s)
Antioxidantes/farmacología , Biopterinas/análogos & derivados , Encéfalo/efectos de los fármacos , Dihidroxifenilalanina/metabolismo , Tirosina/farmacología , Animales , Biopterinas/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Macaca mulatta , Factores de TiempoRESUMEN
The regional brain kinetics of the two enantiomers of the NMDA channel blocker ketamine radiolabelled with 11C was studied in the Rhesus monkey by means of positron emission tomography (PET). The uptake in brain areas which showed high radioactivities was blocked in a dose-dependent manner for both 11C-labelled enantiomers with simultaneous doses of the respective unlabelled (S)- or (R)-ketamine, indicating specific binding. The binding in the striatum and cortical areas of (S)-[N-methyl-11C]ketamine was selective and displaceable by the (R)-enantiomer and by MK-801.
Asunto(s)
Encéfalo/metabolismo , Ketamina/análogos & derivados , Radiofármacos/farmacocinética , Animales , Unión Competitiva , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono/farmacocinética , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Ketamina/metabolismo , Ketamina/farmacocinética , Macaca mulatta , Masculino , Ensayo de Unión Radioligante , Cintigrafía , Receptores de N-Metil-D-Aspartato/metabolismo , Estereoisomerismo , Distribución TisularRESUMEN
The objective of this study was to mimic in a simple experiment the two major brain insults sustained by the patient with a subarachnoid hemorrhage, that is, the ictus and the subsequent delayed reduction of focal cerebral blood flow caused by vasospasm without the interference of subarachnoid blood, to test the hypothesis that ictal events not related to the presence of blood in the subarachnoid space per se may be important for the development of ischemic deficits and cerebral infarction when vasospasm develops. Groups of rats were subjected to a sudden transient elevation of the intracranial pressure to a level causing a brief period of complete global ischemia by infusion of mock cerebrospinal fluid into the cisterna magna (this manipulation was designed to allow survival of the animal and recovery of consciousness). Two and one-half hours later, a focal ischemic insult was induced by occlusion of the middle cerebral artery. Rats subjected to middle cerebral artery occlusion alone and sham operation served as controls. The infarct size was used as the end point and was calculated on brain slices stained with 2,3,5-triphenyltetrazolium chloride. The study demonstrates that a brief sudden elevation in intracranial pressure, in itself consistent with survival and recovery, increased the vulnerability of the brain to a subsequent focal ischemic insult. Thus the combination of insults resulted in significantly (P less than 0.05) larger infarcts than did middle cerebral artery occlusion alone. Further, this combination of insults resulted in a disproportionate enlargement of the affected hemisphere, which could not be explained by the increased infarct size alone.
Asunto(s)
Edema Encefálico/fisiopatología , Infarto Cerebral/fisiopatología , Presión Intracraneal/fisiología , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Daño Encefálico Crónico/patología , Daño Encefálico Crónico/fisiopatología , Edema Encefálico/patología , Infarto Cerebral/patología , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/fisiopatología , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/fisiopatología , Masculino , Ratas , Ratas Endogámicas , Rotura Espontánea , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/fisiopatologíaRESUMEN
The authors have developed a method for routine monitoring of disturbances in brain energy metabolism and extracellular levels of excitatory amino acids using intracerebral microdialysis in 10 patients with subarachnoid hemorrhage. Microdialysis was conducted for periods ranging from 6 to 11 days after ictus. Altogether, 16,054 chemical analyses from 1647 dialysate samples were performed. Concentrations of the energy-related substances lactate, pyruvate, glucose, and hypoxanthine were measured, and the lactate/pyruvate ratio was calculated. The excitatory amino acids glutamate and aspartate were measured. The microdialysis data were matched with computerized tomography findings, clinical course, and outcome. The results support the concepts that microdialysis is a promising tool for chemical monitoring of the human brain and that extracellular fluid levels of lactate, lactate/pyruvate ratio, glucose, hypoxanthine, and glutamate are useful markers of disturbances in brain energy metabolism in neurointensive care patients. These results have generated a working hypothesis that the pattern of these extracellular markers may help differentiate between various causes of energy perturbations, such as hypoxia and different degrees of ischemia. The correlation between the dialysate levels of excitatory amino acids and outcome supports the concept of glutamate receptor overactivation in acute human brain injury.
Asunto(s)
Microdiálisis , Hemorragia Subaracnoidea/metabolismo , Anciano , Ácido Aspártico/metabolismo , Química Encefálica , Femenino , Ácido Glutámico/metabolismo , Humanos , Hipoxantina , Hipoxantinas/metabolismo , Lactatos/metabolismo , Masculino , Persona de Mediana Edad , Hemorragia Subaracnoidea/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The aim of this study was to explore the usefulness of extracellular markers of cerebral ischaemia. Cortical microdialysate concentrations of the energy related metabolites lactate, pyruvate, glucose, adenosine, inosine, hypoxanthine and xanthine, were measured in rats subjected to repeated transient ischaemia. The animals were subjected to one or two 10-min periods of global ischaemia produced by induced intracranial hypertension, with a 2 h period of reperfusion after each insult. In addition, the effect of superimposed secondary hypoxaemia and hypotension was studied. In general, there was a good agreement between the extracellular markers and known intracellular energy disturbances under similar conditions, including marked transient increases of lactate, lactate/pyruvate ratio, inosine and hypoxanthine. Several new observations were made: (1) glucose appeared to be a useful marker of severe ischaemia and recirculation, (2) a marked post-ischaemic xanthine formation was observed implicating a substantial loss of salvageable hypoxanthine as well as increased production of superoxide radicals, (3) a blunted purine response was noted after the second insult, reflecting a reduced intracellular adenine nucleotide pool, and (4) a different pattern of ischaemia markers was observed during secondary hypoxia as compared to hypoxia with hypotension. In conclusion, extracellular lactate, pyruvate, glucose, adenosine, inosine hypoxanthine and xanthine all seem valuable as ischaemia markers. The results support the usefulness of intracerebral microdialysis for monitoring of energy metabolic disturbances caused by cerebral ischaemia/hypoxia. The pattern of extracellular ischaemia markers may help differentiate between various causes of energy perturbations, such as different degrees of ischaemia and hypoxia.
Asunto(s)
Isquemia Encefálica/diagnóstico , Metabolismo Energético/fisiología , Espacio Extracelular/química , Hipoxia Encefálica/diagnóstico , Microdiálisis , Monitoreo Fisiológico , Animales , Isquemia Encefálica/patología , Corteza Cerebral/patología , Electroencefalografía , Hipoxantina/análisis , Hipoxia Encefálica/patología , Inosina/análisis , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/patología , Ácido Láctico/análisis , Masculino , Ácido Pirúvico/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Brain interstitial glycerol was studied as a potential marker for membrane phospholipid degradation in acute human brain injury. METHODS: Glycerol was measured in microdialysis samples from the frontal lobe cortex in four patients in the neurointensive care unit, during the acute phase after severe aneurysmal subarachnoid haemorrhage. Microdialysis probes were inserted in conjunction with a ventriculostomy used for routine intracranial pressure monitoring. Clinical events involving hypoxia/ischaemia were diagnosed by neurological signs, neuroimaging (CT and PET), and neurochemical changes of the dialysate-for example, lactate/pyruvate ratios and hypoxanthine concentrations. RESULTS: Altogether 1554 chemical analyses on 518 microdialysis samples were performed. Clinical events involving secondary hypoxia/ischaemia were generally associated with pronounced increases (up to 15-fold) of the dialysate glycerol concentration. In a patient with a stable condition and no signs of secondary hypoxia/ischaemia the glycerol concentration remained low. Simultaneous determination of glycerol in arterial plasma samples showed that the changes in brain interstitial glycerol could not be attributed to systemic changes and an injured blood brain barrier. CONCLUSIONS: This study suggests that membrane phospholipid degradation occurs in human cerebral ischaemia. Interstitial glycerol harvested by microdialysis seems to be a promising tool for monitoring of membrane lipolysis in acute brain injury. The marker may be useful for studies on cell membrane injury mechanisms mediated by for example, Ca2+ disturbances, excitatory amino acids, and reactive oxygen species; and in the evaluation of new neuroprotective therapeutic strategies.
Asunto(s)
Isquemia Encefálica/metabolismo , Glicerol/análisis , Hipoxia Encefálica/metabolismo , Lipólisis , Lípidos de la Membrana/metabolismo , Fosfolípidos/metabolismo , Hemorragia Subaracnoidea/complicaciones , Enfermedad Aguda , Anciano , Biomarcadores/análisis , Barrera Hematoencefálica , Química Encefálica , Isquemia Encefálica/etiología , Femenino , Glicerol/metabolismo , Humanos , Hipoxia Encefálica/etiología , Aneurisma Intracraneal/complicaciones , Masculino , Microdiálisis , Persona de Mediana Edad , Monitoreo Fisiológico , Reproducibilidad de los ResultadosRESUMEN
This study addresses the issue of endpoint selection in the evaluation of neuroprotective drugs in experimental focal ischaemia. Previous work with the permanent middle cerebral artery (MCA) occlusion model in the rat has demonstrated that the ischaemic lesion does not acquire its final appearance until at least 28 days after the ictus. Therefore, the effect of the NMDA receptor blocker MK-801 (dizocilpine maleate) was evaluated both early (3 days) and late (28 days) after MCA occlusion to determine if the previously reported protective effect of a single post-ischaemic dose of MK-801 found in acute experiments remained after 28 days. Mk-801 (0.5 mg/kg, i.v.) or isotonic saline was randomly given to rats 30 min after MCA occlusion. Infarct volume and volume of ipsilateral and contralateral hemispheres were estimated from camera lucida drawings of 8 defined coronal histological sections of the brain. As expected, a 40% (p < 0.05) reduction of infarct size was found in MK-801 treated rats after 3 days. In animals evaluated 28 days after MCA occlusion, no significant difference in infarct size, total tissue loss (infarct volume+ipsilateral hemisphere atrophy) or remaining non-infarcted tissue (contralateral hemisphere--total tissue loss) was seen between the MK-801 and placebo treated rats. The results suggest that the single dose treatment with MK-801 postponed the evolution of the infarct, which at 3 days after MCA occlusion is still in progress, possibly by ameliorating oedema formation. It remains to be shown if a multiple dose treatment with NMDA receptor antagonists improves the final neuropathological outcome after experimental stroke.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Isquemia Encefálica/patología , Infarto Cerebral/patología , Maleato de Dizocilpina/farmacología , Animales , Atrofia , Edema Encefálico/patología , Corteza Cerebral/patología , Dominancia Cerebral/fisiología , Procesamiento de Imagen Asistido por Computador , Infusiones Intravenosas , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The effect of the antioxidant drug tirilazad mesylate (U-74006F) on histopathological and neurological outcome 3 days after permanent middle cerebral artery (MCA) occlusion was evaluated in rats. Several previous studies have demonstrated the efficacy of tirilazad in reducing infarct size when administered before and during MCA occlusion, whereas post-treatment may be less effective in permanent focal ischaemia. We sought to determine if a protective effect of tirilazad could be demonstrated when administered after the insult only. U-74006F (3 mg/kg, i.v.) or sterile vehicle, was randomly given to rats 10 minutes and 3 hours after permanent MCA occlusion produced by transcranial proximal electrocauterization. Infarct volume and hemisphere volumes were estimated blindly from histological sections of defined levels of the brain after 72 h of ischaemia. Neurological score was determined blindly 1, 2, and 3 days after insult. There was no significant difference in infarct volume, volume of non-infarcted tissue, or neurological score between the tirilazad and placebo-treated rats. In conclusion, our results support the conception that post-treatment with tirilazad mesylate is not efficacious in reducing infarct size in permanent focal ischaemia, while pre-treatment, as reported by other groups, appears to be effective in both permanent and temporary focal ischaemia models. In temporary focal ischaemia, the limited data available suggest that also post-treatment with tirilazad may prove to be neuroprotective.
Asunto(s)
Infarto Cerebral/fisiopatología , Depuradores de Radicales Libres/farmacología , Peróxidos Lipídicos/antagonistas & inhibidores , Pregnatrienos/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Infarto Cerebral/patología , Masculino , Examen Neurológico/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To evaluate interstitial glycerol as a marker of ischaemia by studying the changes in glycerol in direct relation to changes in regional cerebral metabolic rate of oxygen (CMRO(2)), the lactate/pyruvate ratio (LP ratio), and glutamate. METHODS: Transorbital 2 hour middle cerebral artery occlusion (MCAO) was performed in eight monkeys, which were studied with continuous microdialysis for 24 hours. Interstitial fluids were collected by microdialysis and analysed for glycerol, lactate, pyruvate, and glutamate with an enzymatic assay and high performance liquid chromatography. Sequential PET studies of cerebral blood flow (CBF), CMRO(2), oxygen extraction ratio (OER), and cerebral blood volume (CBV) were performed. The microdialysis probe regions were classified as severe ischaemia or penumbra, depending on whether the mean CMRO(2) side to side ratio was below or above 60%, respectively. RESULTS: A nine-fold, sustained increase in glycerol was registered after MCAO in severe ischaemia regions. In penumbra regions, the increase in glycerol was five-fold, but the glycerol concentration returned to baseline within 8 hours of clip removal. The difference between severe ischaemia and penumbra glycerol values was statistically significant. As expected from previous studies, the interstitial LP ratio and glutamate increased markedly in severe ischaemia, with a less pronounced change in penumbra regions. There was a time lag between the biochemical changes in severe ischaemia regions, with the LP ratio preceding glutamate, followed by glycerol. CONCLUSIONS: A marked, sustained increase in interstitial glycerol is indicative of severe ischaemia in this stroke model. A transient, diminutive increase in interstitial glycerol may reflect a penumbra situation. Interstitial glycerol in combination with other biochemical markers such as the LP ratio and glutamate may be useful for clinical monitoring of the ischaemic brain, reflecting a sequence of secondary pathophysiological events.
Asunto(s)
Daño Encefálico Crónico/diagnóstico por imagen , Espacio Extracelular/diagnóstico por imagen , Glicerol/metabolismo , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Daño por Reperfusión/diagnóstico por imagen , Tomografía Computarizada de Emisión , Animales , Ácido Glutámico/metabolismo , Ácido Láctico/metabolismo , Macaca mulatta , Microdiálisis , Consumo de Oxígeno/fisiología , Fosfolípidos/metabolismo , Ácido Pirúvico/metabolismoRESUMEN
BACKGROUND: Due to a few reports of cerebral dysfunction in connection with isoflurane-induced hypotension and concomitant hypocapnia, positron emission tomography (PET) was used to measure cerebral oxygenation and blood flow during similar conditions with isoflurane or propofol. METHODS: The short-lived radionuclide 15O was used for measurement of cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF) and oxygen extraction ratio (OER) regionally in rhesus monkeys during normotensive/normocapnic and hypotensive/hypocapnic conditions, mean arterial pressure 100-110 and 50-65 mmHg and PaCO2 4.4-5.4 and 3.4-4.4 kPa, respectively. Isoflurane or propofol anaesthesia was given (n = 4 in both groups), supported with 70% nitrous oxide and preceded by ketamine anaesthesia (baseline). RESULTS: PET revealed wide variations in CBF between regions during isoflurane anaesthesia, particularly in comparison with propofol anaesthesia, while rCMRO2 decreased globally in a dose-dependent manner during both isoflurane and propofol anaesthesia. The metabolism-flow coupling was intact during propofol but not during isoflurane anaesthesia. Hypotension reduced rCBF, and rOER increased globally with both study drugs when changing from normo- to hypotension. However, this rOER increase was not significant when using PaCO2 as a covariate, and rOER was never above an arbitrary limit for hypoxia of 70%. Thus, hypocapnia, rather than hypotension, was responsible for the somewhat higher rOER measured. CONCLUSION: PET indicated adequate cerebral oxygenation during isoflurane and propofol anaesthesia, despite disparate blood-flow patterns. Hypotension and concomitant moderate hyperventilation reduced rCBF, but did not result in hypoxia.
Asunto(s)
Anestesia , Anestésicos Intravenosos/farmacología , Encéfalo/metabolismo , Circulación Cerebrovascular , Hipocapnia , Hipotensión Controlada , Oxígeno/sangre , Propofol/farmacología , Tomografía Computarizada de Emisión , Anestésicos Disociativos/farmacología , Anestésicos por Inhalación/farmacología , Animales , Encéfalo/diagnóstico por imagen , Isoflurano/farmacología , Ketamina/farmacología , Macaca mulatta , Consumo de OxígenoRESUMEN
BACKGROUND: General anaesthesia impairs the gas exchange in the lungs, and moderate desaturation (SaO2 86-90%) occurred in 50% of anaesthetised patients in a blinded pulse oximetry study. A high FiO2 might reduce the risk of hypoxaemia, but can also promote atelectasis. We hypothesised that a moderate positive end-expiratory pressure (PEEP) level of 10 cmH2O can prevent atelectasis during ventilation with an FiO2 = 1.0. METHODS: Atelectasis was evaluated by computed tomography (CT) in 13 ASA I-II patients undergoing elective surgery. CT scans were obtained before and 15 min after induction of anaesthesia. Then, recruitment of collapsed lung tissue was performed as a "vital capacity manoeuvre" (VCM, inspiration with Paw = 40 cmH2O for 15 s), and a CT scan was obtained at the end of the VCM. Thereafter, PEEP = 0 cmH2O was applied in group 1, and PEEP = 10 cmH2O in group 2. Additional CT scans were obtained after the VCM. Oxygenation was measured before and after the VCM. RESULTS: Atelectasis (> 1 cm2) was present in 12 of the 13 patients after induction of anaesthesia. At 5 and 10 min after the VCM, atelectasis was significantly smaller in group 2 than group 1 (P < 0.005). A significant inverse correlation was found between PaO2 and atelectasis. CONCLUSIONS: PEEP = 10 cmH2O reduced atelectasis formation after a VCM, when FiO2 = 1.0 was used. Thus, a VCM followed by PEEP = 10 cmH2O should be considered when patients are ventilated with a high FiO2 and gas exchange is impaired.
Asunto(s)
Anestesia General/efectos adversos , Oxígeno/administración & dosificación , Respiración con Presión Positiva , Atelectasia Pulmonar/etiología , Atelectasia Pulmonar/prevención & control , Adulto , Anciano , Femenino , Humanos , Capacidad Inspiratoria , Pulmón/diagnóstico por imagen , Rendimiento Pulmonar , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Respiración con Presión Positiva/métodos , Atelectasia Pulmonar/diagnóstico por imagen , Atelectasia Pulmonar/fisiopatología , Intercambio Gaseoso Pulmonar , Tomografía Computarizada por Rayos X , Capacidad VitalRESUMEN
A major cause of impaired gas exchange during general anaesthesia is atelectasis, causing pulmonary shunt. A 'vital capacity' (VC) manoeuvre (i.e. inflation of the lungs up to 40 cm H2O, maintained for 15 s) may re-expand atelectasis and improve oxygenation. However, such a manoeuvre may cause adverse cardiovascular effects. Reducing the time of maximal inflation may improve the margin of safety. The aim of this study was to analyse the change over time in the amount of atelectasis during a VC manoeuvre in 12 anaesthetized adults with healthy lungs. I.v. anaesthesia with controlled mechanical ventilation (VT 9 (SD 1) ml kg-1) was used. For the VC manoeuvre, the lungs were inflated up to an airway pressure (Paw) of 40 cm H2O. This pressure was maintained for 26 s. Atelectasis was assessed by analysis of computed x-ray tomography. The amount of atelectasis, measured at the base of the lungs, was 4.0 (SD 2.7) cm2 after induction of anaesthesia. The decrease in the amount of atelectasis over time during the VC manoeuvre was described by a negative exponential function with a time constant of 2.6 s. At an inspired oxygen concentration of 40%, PaO2 increased from 17.2 (4.0) kPa before to 22.2 (6.0) kPa (P = 0.013) after the VC manoeuvre. Thus in anaesthetized adults undergoing mechanical ventilation with healthy lungs, inflation of the lungs to a Paw of 40 cm H2O, maintained for 7-8 s only, may re-expand all previously collapsed lung tissue, as detected by lung computed tomography, and improve oxygenation. We conclude that the previously proposed time for a VC manoeuvre may be halved in such subjects.
Asunto(s)
Anestesia General/efectos adversos , Atelectasia Pulmonar/terapia , Respiración Artificial/métodos , Adulto , Anciano , Presión del Aire , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Presión Parcial , Atelectasia Pulmonar/diagnóstico por imagen , Atelectasia Pulmonar/etiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Capacidad VitalRESUMEN
OBJECTIVE: to evaluate the predictive value of measurements of regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction ratio (OER) for assessment of the fate of ischemic brain tissue. MATERIALS AND METHODS: Sequential PET measurements were performed during middle cerebral artery occlusion (MCAO; 2 h) and 12-24 h (mean 18 h) of reperfusion in a primate model (Macaca mulatta, n = 8). A penumbra region was delineated on the MCAO PET image (OER > 125% and CMRO2> or = 45% of the values observed in the contralateral hemisphere, respectively) and an infarction region was delineated on the last PET image (CMRO2 <45% of the values observed in the contralateral hemisphere). The penumbra regions delineated during MCAO and the infarction regions delineated at the final PET, were copied on to the images from all other PET sessions for measurements of CBF, CMRO2 and OER. Ratios were calculated by dividing the mean values obtained by the values of the corresponding contralateral region. RESULTS: Histopathology verified the adequacy of the criteria applied in the last PET for delineation of the infarction region. The penumbra region and infarction region were separated in all cases, except in two cases where a minimal overlap was seen. CBF and OER showed considerable variation over time and there was no consistent difference between the penumbra and infarction regions. CMRO2 showed a more stable pattern and the difference between penumbra and infarction regions was maintained from the time of MCAO throughout the entire reperfusion phase. With CMRO2 as predictor, all 50 observations could be correctly predicted as penumbra or infarction when using an optimal threshold ratio value estimated to be in the interval of 61% to 69% of the corresponding contralateral region. CBF and OER proved to have low power as predictors. CONCLUSIONS: The results indicate that CMRO2 is the best predictor of reversible or irreversible brain damage and the critical metabolic threshold level appears to be a reduction of oxygen metabolism to between 61% and 69% of the corresponding contralateral region.