Safe prognostication following cardiac arrest: The role of the pharmacokinetics of fentanyl in patients treated with targeted temperature management.

BACKGROUND: Neurological prognostication following cardiac arrest (CA) is complex and sedative agents may significantly impair responses to clinical examination. This study investigates the elimination of fentanyl in patients treated with targeted temperature management (TTM). METHODS: We measured the blood concentration of fentanyl in 23 post-cardiac arrest patients treated with TTM following discontinuation of continuous infusion. Fentanyl was discontinued when the patients were rewarmed to a temperature of 36-36.5 °C and a blood sample taken 12 h later. Measured concentrations were compared with predicted concentrations using population pharmacokinetic parameters. Variables likely to prolong half-life were analysed using a multivariate regression model. RESULTS: We found a statistically significant difference between median measured and predicted concentrations (measured 0.93 µg/L [range 0.11-8.29 µg/L] vs. predicted 0.30 µg/L [range 0.16-0.59 µg/L]; p < 0.05). Univariate analysis identified a significant relationship between estimated fentanyl half-life and serum lactate concentrations (r = 0.45, p < 0.05). Multivariate linear regression identified two variables (SAPS score and genotype), which together were able to explain approximately 30 % of the variation in the population (adjusted R2 = 0.3177, p = 0.0194). No significant relationships were found between fentanyl half-life and patients' clinical or biochemical variables or co-administration of drugs metabolized by cytochrome p450. CONCLUSIONS: There is marked variation in the clearance of fentanyl following continuous infusion during TTM after CA which correlates with illness severity, lactate concentration and genetic polymorphisms of the cytochrome p450 liver enzymes. Sustained presence of fentanyl may influence response to neurological examination at 12 h post discontinuation in patients receiving the drug as an infusion as part of TTM.

The Natural Historian's Guide to the CT Galaxy: Step-by-Step Instructions for Preparing and Analyzing Computed Tomographic (CT) Data Using Cross-Platform, Open Access Software.

The decreasing cost of acquiring computed tomographic (CT) data has fueled a global effort to digitize the anatomy of museum specimens. This effort has produced a wealth of open access digital three-dimensional (3D) models of anatomy available to anyone with access to the Internet. The potential applications of these data are broad, ranging from 3D printing for purely educational purposes to the development of highly advanced biomechanical models of anatomical structures. However, while virtually anyone can access these digital data, relatively few have the training to easily derive a desirable product (e.g., a 3D visualization of an anatomical structure) from them. Here, we present a workflow based on free, open source, cross-platform software for processing CT data. We provide step-by-step instructions that start with acquiring CT data from a new reconstruction or an open access repository, and progress through visualizing, measuring, landmarking, and constructing digital 3D models of anatomical structures. We also include instructions for digital dissection, data reduction, and exporting data for use in downstream applications such as 3D printing. Finally, we provide Supplementary Videos and workflows that demonstrate how the workflow facilitates five specific applications: measuring functional traits associated with feeding, digitally isolating anatomical structures, isolating regions of interest using semi-automated segmentation, collecting data with simple visual tools, and reducing file size and converting file type of a 3D model.

PORTUGUÊS (PORTUGUESE)  O Guia da Galáxia da Tomografia Computadorizada para um Biólogo: instruções passo a passo para preparar e analisar dados tomográficos usando um software gratuito de acesso aberto  Thaddaeus J. Buser, Olivia F. Boyd, Álvaro Cortés, Cassandra M. Donatelli, Matthew A. Kolmann, Jennifer L. Luparell, Janne A. Pfeiffenberger, Brian L. Sidlauskas, Adam P. Summers  RESUMOO custo decrescente da obtenção de dados de Tomografia Computadorizada (TC) alimentou um esforço global para digitalizar espécimes depositados em museus. Esse esforço produziu uma grande variedade de modelos digitais 3 D com dados de anatomia, disponíveis para qualquer pessoa com acesso à Internet. As aplicações potenciais desses dados são amplas, desde a impressão 3 D para fins puramente educacionais, até o desenvolvimento de modelos biomecânicos de estruturas anatômicas altamente avançados. No entanto, enquanto praticamente qualquer pessoa pode acessar esses dados digitais, relativamente poucos têm o treinamento para obter facilmente um produto de interesse (por exemplo, uma visualização 3 D de uma estrutura anatômica). Aqui, apresentamos um tutorial baseado em um software gratuito de código aberto e multiplataforma para o processamento de dados de TC. Fornecemos instruções passo a passo que começam com a obtenção de dados de TC a partir de uma nova reconstrução ou num repositório de acesso aberto, e progredimos através da visualização, medição, marca de referência e construção de modelos digitais 3 D de estruturas anatômicas. Também incluímos instruções para dissecação digital, redução de dados e exportação de dados para uso em aplicativos posteriores, como os de impressoras 3 D. Por fim, fornecemos vídeos e tutoriais suplementares que demonstram como o tutorial facilita cinco aplicações específicas: medir características funcionais associadas à alimentação, isolar estruturas anatômicas digitalmente, isolar regiões de interesse usando segmentação semi-automática, coletar dados com ferramentas visuais simples, e reduzir o tamanho de arquivo e converter o tipo de arquivo do modelo 3 D.

FRANÇAIS (FRENCH)  Guide de l'historien de la nature à travers la galaxie TDM: instructions étape par étape pour la préparation et l'analyse de données tomodensitométrique (TDM) à l'aide d'un logiciel à accès ouvert multiplateforme Thaddaeus J. Buser, Olivia F. Boyd, Álvaro Cortés, Cassandra M. Donatelli, Matthew A. Kolmann, Jennifer L. Luparell, Janne A. Pfeiffenberger, Brian L. Sidlauskas, Adam P. Summers RÉSUMÉLe coût décroissant de l'acquisition de données tomodensitométriques (TDM) a alimenté un effort mondial pour numériser l'anatomie des spécimens de musée. Cet effort a produit une multitude de modèles d'anatomie numérique 3 D en accès libre accessibles à tous ceux qui ont accès à Internet. Les applications potentielles de ces données sont vastes, allant de l'impression 3 D à des fins purement pédagogiques au développement de modèles biomécaniques de structures anatomiques très avancés. Cependant, alors que pratiquement tout le monde peut accéder à ces données numériques, relativement peu ont la formation nécessaire pour en tirer facilement un produit intéressant (par exemple, une visualisation 3 D d'une structure anatomique). Ici, nous présentons un flux de travail basé sur un logiciel gratuit, à accès ouvert et multiplateforme pour le traitement des données TDM. Nous fournissons des instructions étape par étape qui commencent par l'acquisition de données TDM à partir d'une nouvelle reconstruction ou d'un référentiel en accès gratuit, et progressent à travers la visualisation, la mesure, le marquage et la construction de modèles numériques 3 D de structures anatomiques. Nous incluons également des instructions pour la dissection numérique, la réduction des données et l'exportation de données à utiliser dans des applications en aval telles que l'impression 3 D. Enfin, nous proposons des vidéos et des workflows supplémentaires qui montrent comment le workflow facilite cinq applications spécifiques: mesurer les traits fonctionnels associés à l'alimentation, isoler numériquement les structures anatomiques, isoler les régions d'intérêt à l'aide de la segmentation semi-automatisée, collecter des données avec des outils visuels simples, réduire la taille du fichier et convertir le type de fichierd'un modèle 3 D.

Characterization of Differentiated SH-SY5Y as Neuronal Screening Model Reveals Increased Oxidative Vulnerability.

The immortalized and proliferative cell line SH-SY5Y is one of the most commonly used cell lines in neuroscience and neuroblastoma research. However, undifferentiated SH-SY5Y cells share few properties with mature neurons. In this study, we present an optimized neuronal differentiation protocol for SH-SY5Y that requires only two work steps and 6 days. After differentiation, the cells present increased levels of ATP and plasma membrane activity but reduced expression of energetic stress response genes. Differentiation results in reduced mitochondrial membrane potential and decreased robustness toward perturbations with 6-hydroxydopamine. We are convinced that the presented differentiation method will leverage genetic and chemical high-throughput screening projects targeting pathways that are involved in the selective vulnerability of neurons with high energetic stress levels.

The dependency of oxygen consumption on oxygen delivery in critically ill postoperative patients is mimicked by variations in sedation.

The finding of a dependence of oxygen consumption on oxygen delivery in critically ill patients has encouraged interventions to increase oxygen delivery index (DO2I) to overcome tissue hypoxia. In individuals other factors may influence oxygen consumption index (VO2I) and DO2I and may cause an apparently dependent relationship. We studied the effects of sedation and temperature on the VO2I/DO2I relationship in 13 perioperative patients. Pooled data showed significant correlations between VO2I and DO2I (r greater than 0.6, p less than 0.05) but also between VO2I and sedation score (r greater than 0.7, p less than 0.05), but not VO2I and temperature (r less than 0.5). When VO2I was standardized for the effects of sedation score (SS), the relationship between VO2I and DO2I was lost (r less than 0.5). Seven of 13 patients had significant (p less than 0.05) correlations between VO2I and SS and six of 13 between VO2I and DO2I; when standardized for the effect of varying sedation, no relationships were significant. When interpreting oxygen transport data from critically ill patients, the effects of sedation but not temperature must be taken into account; otherwise a false impression of a dependent relationship between VO2I and DO2I may cause unnecessary treatment.

Cell-free plasma DNA as a prognostic marker in intensive treatment unit patients.

Recent evidence suggests that cell-free plasma DNA has potential use as a prognostic marker in many clinical settings. The aim of the present study was to evaluate the prognostic role of cell-free plasma DNA in the prediction of clinical outcome in intensive treatment unit (ITU) patients. Cell-free plasma DNA was measured by real-time polymerase chain reaction assay for the beta-globin gene and SOFA score, APACHE II score, CRP concentrations, and clinical outcome (duration of stay, ventilation time, and mortality) were noted in 94 patients on admission to the ITU. The median plasma DNA concentration in ITU patients was 5493 GE/mL and this was significantly (P <0.001) higher than the DNA concentration in healthy subjects (1970 GE/mL). DNA concentration demonstrated a significant correlation with serum C-reactive protein (CRP) (r = 0.363) concentration and Sepsis-related Organ Failure Assessment (SOFA) (r = 0.360) score (P <0.001 for both by Pearson correlation) but not with Acute Physiology And Chronic Health Evaluation (APACHE II) score. Patients on ventilation had significantly higher DNA concentrations compared to nonventilated patients (7362 GE/mL versus 4479 GE/mL; P = 0.004). The median DNA concentration in nonsurvivors was 9148 GE/mL, and this was 2.3-fold greater than that in survivors (3921 GE/ml, P <0.001). ROC analysis of the data indicated a sensitivity of 85% and a specificity of 80% when DNA concentration of 6109 GE/mL was taken as a predictor of death. The data suggest that cell-free plasma DNA concentration is potentially useful as a prognostic marker in ITU patients.

A cost analysis of a treatment policy of a deliberate perioperative increase in oxygen delivery in high risk surgical patients.

OBJECTIVE: To investigate the cost implications of a treatment policy of a deliberate perioperative increase of oxygen delivery in high risk surgical patients. DESIGN: A cost-effectiveness analysis comparing 'protocol' high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min/m2 with 'control' patients. INTERVENTIONS: In a randomised, controlled clinical trial we previously demonstrated a significant reduction in mortality (5.7% vs 22.2%, p = 0.015) and morbidity (0.68 +/- 0.16 complications vs 1.35 +/- 0.20, p = 0.008) in 'protocol' high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min per m2 compared with 'control' patients. This current study retrospectively analysed the medical care and National Health Service resource use of each patient in the trial. Departmental purchasing records and business managers were consulted to identify the unit cost of these resources, and thereby the cost of treating each patient was calculated. RESULTS: The median cost of treating a protocol patient was lower than for a control patient (6,525 pounds vs 7,784 pounds) and this reduction was due mainly to a decrease in the cost of treating postoperative complications (median 213 pounds vs 668 pounds). The cost of obtaining a survivor was 31% lower in the protocol group. CONCLUSION: Perioperative increase of oxygen delivery in high risk surgical patients not only improves survival, but also provides an actual and relative cost saving. This may have important implications for the management of these patients and the funding of intensive care.

Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval.

OBJECTIVE: To investigate the time course of changes in follicular fluid (FF) concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal oocyte collection. STUDY DESIGN: Forty-five patients with tubal infertility were randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for sedation during ultrasound-guided transvaginal oocyte collection. Paracervical block with lignocaine was given for analgesia. Simultaneous blood and FF samples were drawn at 5-minute intervals after the bolus dose for analysis of drug levels. RESULTS: Data were obtained on 15 women receiving midazolam and fentanyl and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak and then fell in an exponential fashion as was expected. The FF levels of the agents continued to rise significantly to 25 minutes after the bolus dose, although the absolute level was low when compared with the blood level. There were no significant differences in fertilization or pregnancy rates in the three groups, but patient numbers were small. CONCLUSION: We conclude that midazolam, fentanyl, and alfentanil are found in FF after a single IV dose, but further investigation needs to be undertaken to investigate any potential influence on fertilization and implantation rates.

Optimisation of oxygenation and tissue perfusion in surgical patients.

Surgical patients with limited cardiovascular reserve have much worse prognosis than patients with normal hearts. This review identifies 17 randomised controlled clinical trials that have investigated peri-operative therapy designed to increase tissue perfusion in surgical patients, many of whom have limited cardiovascular reserve. Although there are differences which make equating the trials complex, a total of 1974 patients have been enrolled in the studies and the odds ratio for reduction in mortality is 0.45 (95% confidence intervals 0.33-0.60). Further research needs to be undertaken in the identification of patients with limited cardiovascular reserve and for investigating proposed treatment strategies. Despite this, it appears that such patients have improved outcome if they are admitted to intensive care unit pre-operatively and have suitable therapy given to improve tissue oxygen delivery.

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

The oxygen trail: the goal.

Over the last 10 years, there have been great advances in knowledge concerning changes in tissue perfusion and its prognostic implications. Has this translated into improved patient management? We review the clinical trials that have deliberately increased tissue oxygen delivery by increasing cardiac output. We have divided the studies into those that intervene early or those that intervene late in the course of a patient's illness. Although there are methodological problems limiting interpretation of the results, we show a combined odds ratio of a reduction in mortality for the early studies but not for the late studies. We conclude that a treatment policy whereby oxygen delivery is deliberately increased improves patient outcome if it is initiated early, prior to the onset of organ failure.

Mianserin and complete heart block.

Cardiac complications are common in tricyclic antidepressant poisoning, but are rare with overdose of mianserin, which is a tetracyclic antidepressant. We report a case in which repeated episodes of complete heart block occurred following overdose with mianserin.

Physiological scoring systems and audit.

Scoring systems designed to rate the severity of an illness are being used for comparison of hospital units to identify different standards of care and to allocate resources. One such scoring system is the Acute Physiology and Chronic Health Evaluation (APACHE) system which is designed to assess the severity of illness of patients in intensive care units (ICUs). It is widely assumed that different ICUs can be compared by the ratio of actual mortality to that predicted by the APACHE score. However, we suggest that the use of physiological data that can be influenced by medical and nursing intervention should not be used for audit. For example, by good care a patient may be made less severely ill and, therefore, may have a lower actual mortality while, at the same time, accumulating only a low APACHE score with low predicted mortality. This patient could have, therefore, the same mortality ratio as a patient treated inappropriately, who may have a higher actual mortality and a high APACHE score with greater predicted mortality. Paradoxically, the very accuracy of these scoring systems for assessing the severity of illness precludes their use for comparison and audit.

Enhancement of perioperative tissue perfusion as a therapeutic strategy for major surgery.

Multiple organ dysfunction syndrome (MODS) accounts for most surgical deaths which occur some days postoperatively. Current hypotheses concerning the pathophysiology of MODS place tissue hypoxia and reperfusion as a central feature of the initiation and continuation of the syndrome. Surgical patients are at risk of developing overt and covert tissue hypoxia and hypoperfusion due to anesthetic, surgical, and other factors; and it is known that surgical patients with poor cardiovascular reserve have a worse outcome postoperatively. A number of clinical studies have attempted to intervene early in surgical patients to prophylactically improve tissue perfusion in the perioperative period by augmentation of cardiac output. These studies demonstrate a reduction in mortality and morbidity in these groups of patients. A similar approach has been tried in other groups of critically ill patients, at a later state in the evolution of their illness; these studies have not shown any improvement in outcome. In surgical patients, data show that those with more coexisting pathology and worse cardiac function may benefit most from a treatment approach aimed at improving tissue perfusion; furthermore, this may result in cost savings. The implications for the management of the higher risk surgical patient are obvious. It may no longer be acceptable to undertake surgery in these patients without facilities to monitor and improve cardiac output and tissue perfusion.

The use of dopexamine hydrochloride to increase oxygen delivery perioperatively.

Perioperative increases in oxygen delivery may reduce morbidity and mortality in certain groups of surgical patients. However positive inotropic drugs, such as dobutamine and epinephrine themselves, may increase oxygen demand. Dopexamine hydrochloride is a new dopamine analogue with action at beta 2-adrenoceptors and DA1 receptors, but it possesses no direct alpha-adrenoceptor activity. We assessed the suitability of dopexamine to increase oxygen delivery perioperatively in eight patients having vascular surgery and studied its effects on oxygen demand. Oxygen delivery was increased toward 600 mL.min-1.m-2 by intravenous (IV) fluid infusion and IV titration of dopexamine hydrochloride. Oxygen delivery could be increased preoperatively (375 +/- 43 to 552 +/- 50 mL.min-1.m-2, P < 0.05) with > 600 mL.min-1.m-2 being achieved in five patients. This increase was achieved without significant increase in total body oxygen consumption (114 +/- 10 to 123 +/- 7 mL.min-1.m-2 P > 0.05) or rate pressure product (13.7 +/- 2.8 x 10(3) to 13.5 +/- 2.1 x 10(3) mm Hg.beats/min, P > 0.05). Postoperatively oxygen delivery was increased again without an increase in oxygen consumption (126 +/- 10 mL.min-1.m-2, P > 0.05) or rate pressure product (14.2 +/- 0.9 x 10(3) mm Hg.beats/min, P > 0.05). Dopexamine hydrochloride may provide a method for increasing oxygen delivery perioperatively with only limited increase in total body or myocardial oxygen demand.

A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.

OBJECTIVE: To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery. DESIGN: Prospective, randomized clinical trial. SETTING: A teaching hospital general intensive care unit, London, England. PATIENTS: A total of 107 surgical patients, who were assessed as high risk from previously identified criteria, were studied during an 18-month period. INTERVENTIONS: Patients were randomly assigned to a control group (n = 54) that received best standard perioperative care, or to a protocol group (n = 53) that, in addition, had deliberate increase of oxygen delivery index to greater than 600 mL/min per square meter by use of dopexamine hydrochloride infusion. OUTCOME MEASURES: Mortality and complications were assessed to 28 days postoperatively. RESULTS: Groups were similar with respect to demographics, admission criteria, operation type, and admission hemodynamic variables. Groups were treated similarly to maintain blood pressure, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure; however, once additional treatment with dopexamine hydrochloride had been given, the protocol group had significantly higher oxygen delivery preoperatively (median, 597 vs 399 mL/min per square meter; P < .001) and postoperatively (P < .001). Results indicate a 75% reduction in mortality (5.7% vs 22.2%; P = .015) and a halving of the mean (+/- SEM) number of complications per patient (0.68 [+/- 0.16] vs 1.35 [+/- 0.20]; P = .008) in patients randomized to the protocol group. CONCLUSION: Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients.

Fibrosing alveolitis due to sulphasalazine in a patient with rheumatoid arthritis.

Rheumatoid arthritis is being increasingly treated with sulphasalazine. We report the first case of a patient being treated for rheumatoid arthritis who developed severe dyspnoea with chest radiograph shadowing, reversible on discontinuation of sulphasalazine and subsequent steroid therapy. An histological diagnosis of fibrosing alveolitis was made. Thirteen cases of similar reactions to sulphasalazine, all in patients treated for inflammatory bowel disease, can be found in the literature. We identify two types of pulmonary reaction, an eosinophilic pneumonitis and a fibrosing alveolitis. Adequate histological investigation is needed to differentiate between the two and management may be different. The diagnosis of pulmonary reactions are important because they can be easily confused with complications of the underlying disease but the prognosis is much better.

Effects of insertion depth and use of the sidearm of the introducer sheath of pulmonary artery catheters in cardiac output measurement.

OBJECTIVE: To investigate the effects of various insertion depths and sidearm functions of the introducer sheath of pulmonary artery flotation catheters on cardiac output measurement. DESIGN: Prospective, randomized, crossover study. SETTING: A general intensive care unit. PATIENTS: Ten patients who had a pulmonary artery flotation catheter placed in the right internal jugular vein as part of their clinical management. INTERVENTIONS: Cardiac output was measured at three insertion depths of the pulmonary artery catheter, each with a different rate of flow into the introducer sheath. MEASUREMENTS AND MAIN RESULTS: Significant differences of up to 23% occurred in the measurement of cardiac output under the various conditions. Cardiac output measurement is greater, the closer the injection port lies to the introducer sheath and the more open the introducer sheath sidearm. CONCLUSIONS: All users of pulmonary artery catheters should be alert to this problem. For reliable measurements of cardiac output by thermodilution, the cold saline injection port of the pulmonary artery catheter must be downstream of the introducer sheath, and the introducer sidearm must be closed.

The cardiovascular changes associated with equipotent anaesthesia with either propofol or isoflurane. Particular emphasis on right ventricular function.

The differences in effects of anaesthetic agents on right ventricular function have not been studied. We have developed a cross-over study design to compare the effects of propofol and isoflurane on cardiac and specifically right ventricular function. Ten patients were anaesthetised with equivalent MAC of isoflurane to MIR of propofol. After measurements had been taken on the randomly assigned first agent the patients were crossed over to the other agent and measurements were repeated. Cardiac function was assessed using a pulmonary artery catheter with a fast response thermistor. There were no differences in heart rate or blood pressure between the two agents suggesting that equivalent anaesthetic doses had been given. There were significantly (P < 0.05) higher cardiac output (4.0 to 4.5 l.min-1), right ventricular ejection fraction (35.1 to 39.4%), stroke volume (35.4 to 39.6 ml) and right ventricular end-diastolic volume index (102 to 110 ml.m2-1) with propofol compared to isoflurane. We conclude that propofol results in improved right ventricular performance compared to isoflurane. We have also shown that anaesthetic agents can be compared using a cross-over study design, and have demonstrated that MAC of isoflurane and MIR of propofol can be directly compared. We suggest that propofol may be a more suitable agent than isoflurane for anaesthesia in patients who may already have impaired right ventricular function and in whom maintaining high cardiac output may be beneficial.