Assessment of the plethysmographic variability index as a predictor of fluid responsiveness in critically ill patients: a pilot study.

Optimising intravascular volume in patients with hypotension requiring vasopressor support is a key challenge of critical care medicine. The optimal haemodynamic parameter to assess fluid responsiveness in critically ill patients, particularly those requiring a noradrenaline infusion and mechanical ventilation, remains uncertain. This pilot study assessed the accuracy of the plethysmographic variability index (PVI), (Radical-7 pulse co-oximeter, Masimo®, Irvine, CA, USA) in predicting fluid responsiveness in 25 patients who required noradrenaline infusion to maintain mean arterial pressure over 65 mmHg and were mechanically ventilated with a 'lung-protective' strategy, and whether administering a fluid bolus was associated with a change in PVI (Δ PVI). In this study, fluid responsiveness was defined as an increase in stroke volume of greater than 15% after a 500 ml bolus of colloid infusion over 20 minutes. Of the 25 patients included in the study, only 12 (48%) were considered fluid responders. As static haemodynamic parameters, PVI, central venous pressure and inferior vena cava distensibility index were all inaccurate at predicting volume responsiveness with PVI being the least accurate (area under the receiver operating characteristic curve=0.41, 95% confidence interval 0.18 to 0.65). However, fluid responsiveness was associated with a change in PVI, but not a change in heart rate or central venous pressure. This association between Δ PVI and fluid responsiveness may be a surrogate marker of improved cardiac output following a fluid bolus and warrants further investigation.

Can embryo metabolism be used for selecting bovine embryos before transfer?

The quality of in vitro-produced bovine embryos remains variable. The selection of these embryos based only on their morphology does not allow for acceptable gestational rates to be obtained. The use of metabolic markers to select viable embryos before transfer would be of valuable help, both economically and as a research tool. The ideal marker should meet several conditions: it should be able to be evaluated 1) in a totally non-invasive manner, 2) on individual embryos (which necessitates very sensitive techniques), 3) very rapidly (so that it is compatible with the immediate transfer of fresh embryos), and 4) in order to allow viable embryos to be separated from those that are not viable, whatever the production system used. In practice, such a marker does not exist, but certain methods of metabolic evaluation resemble it. The development of a metabolic marker is confronted by the metabolic characteristics of the embryo, notably the evolution of the metabolism during the development of the embryo and its adaptation to the changes in the environment.

Human tubal fluid: production, nutrient composition and response to adrenergic agents.

Vascularly perfused Fallopian tubes have been used to study the formation and composition of human tubal fluid and the response to adrenergic agents. An artery serving the tube was cannulated and perfused with Medium 199 supplemented with bovine serum albumin (BSA) and antibiotics. A second cannula was attached to the fimbriated end for native tubal fluid collection. The preparation was viable for up to 2 h. Tubal fluid was only obtained in tubes removed in the proliferative and early secretory phases of the ovarian cycle. Isoproterenol (1 mM) added to the perfusate stimulated fluid production, whereas dibutyryl cyclic AMP (1 mM) reduced fluid formation by 66%. Glucose, pyruvate and lactate concentrations in tubal fluid, measured by microfluorescence assays, were 1.11, 0.14 and 5.4 mM respectively. The concentrations of 17 amino acids in tubal fluid were measured by high performance liquid chromatography following fluorescence derivatization. Arginine (0.19 mM) > alanine (0.11 mM) > glutamate (0.09 mM) were present in highest concentration in all phases of the cycle. All 17 amino acid concentrations in tubal fluid were below those in the vascular perfusate. These data provides the basis for a culture medium whose composition mimics the physiological environment to which early human embryos are exposed.

Oxygen uptake and carbohydrate metabolism by in vitro derived bovine embryos.

The consumption of oxygen, uptake of pyruvate and glucose and production of lactate were determined for groups of bovine embryos produced in vitro from the one-cell to the blastocyst stage (day 0-6 of culture). Measurements were made in Hepes-buffered synthetic oviduct fluid medium supplemented with 1.0 mmol pyruvate l-1, 10 mmol D,L-lactate l-1 and 1.5 mmol glucose l-1 and also 3 mg BSA ml-1 and, from day 5 of development, 10% (v/v) fetal calf serum. The amount of ATP production was determined from oxygen consumption and the proportion of glucose taken up that could be accounted for by lactate production. The data revealed that oxygen consumption was relatively constant from days 0-4 of culture (0.24-0.27 nl per embryo h-1), but increased with the initiation of compaction (0.39 nl per embryo h-1) and continued to increase with the formation and expansion of the blastocoel (0.9 nl per embryo h-1). Both pyruvate and glucose uptake followed similar patterns. Furthermore, when plotted against oxygen consumption, both pyruvate and glucose uptake increased significantly (P < 0.001) in a linear relationship (R2 = 0.61 and 0.49, respectively). Lactate production also increased with development and accounted for 40% of glucose uptake at day 0 of culture (putative zygotes), increasing to 70% by day 2 (eight-cell stage) and 100% of glucose uptake from day 4 of culture onwards. ATP production followed a similar pattern to that of oxygen consumption (60-85 pmol per embryo h-1 from day 0 to day 4) increasing with compaction (124 pmol per embryo h-1) and blastulation (221 pmol per embryo h-1). For precompaction stages, 93-96% of ATP production was derived from oxidative phosphorylation, decreasing to 82% with compaction. ATP produced by oxidative phosphorylation could be accounted for by the uptake of pyruvate, suggesting that bovine embryos produced in vitro utilize little endogenous substrates when appropriate exogenous substrates are present in the culture medium. The data revealed that bovine embryos were dependent on oxidative phosphorylation for energy (ATP) production at all stages of pre-elongation development, with perhaps a shift in dependence towards glycolysis in conjunction with compaction. It follows that oxidizable substrates, such as pyruvate and certain amino acids, are preferred in embryo culture medium during development in vitro.

Consumption of amino acids by bovine preimplantation embryos.

Bovine embryos produced in vitro from the putative zygote stage to the blastocyst stage, and blastocysts freshly flushed from the uterus, were cultured in a physiological mixture of amino acids. Depletion of amino acids from the medium and, in a few cases, their appearance, was measured by high performance liquid chromatography. Amino acids were depleted at widely differing rates. The depletion of amino acids was higher when embryos at later developmental stages were cultured, implying an increase in amino acid requirement with development. Threonine was the only amino acid to be depleted at all stages of development; depletion increased from 0.18 +/- 0.07 pmol embryo-1 h-1 at the putative zygote stage to 1.96 +/- 0.49 pmol embryo-1 h-1 at the blastocyst stage. Glutamine was depleted at the putative zygote stage and the 4-cell stage (0.76 +/- 0.05 and 0.94 +/- 0.10 pmol embryo-1 h-1 respectively), but was not significantly depleted at the later stages. Alanine was the only amino acid that appeared consistently in the medium and its production increased progressively throughout development. Aspartate, glutamate, threonine and lysine were depleted significantly by blastocysts derived both in vitro and in vivo; the embryos in vivo also depleted arginine, phenylalanine, isoleucine and tyrosine. These results indicate that individual amino acids are depleted at different rates by bovine preimplantation embryos and suggest that amino acid requirements change during development.

The Purley train crash mechanism: injuries and prevention.

On the afternoon of Saturday 4th March 1989 two trains, both bound for London Victoria Station, collided. Part of the rear train rolled down a steep railway embankment and jack-knifed against a tree. The mechanism of the crash and the injuries sustained by the 55 victims who were seen in the A&E Department of the Mayday University Hospital are described. Improvements in signalling technology and design of rolling stock which may reduce both the risk of collision and severity of injury in future accidents are discussed.