Perioperative metabolic acidosis: The Bradford Anaesthetic Department Acidosis Study.

Metabolic acidosis is considered deleterious but is common in post-surgical patients admitted to intensive care unit. We evaluated the prevalence and time course of metabolic acidosis in elective major surgery, and generated hypotheses about causes, by hourly arterial blood sampling in 92 patients. Metabolic acidosis began before incision and most had occurred by the next hour. Seventy-eight per cent of patients had a significant metabolic acidosis post-operatively. Two overlapping phases were observed. The early phase started before incision, characterised by a rising chloride and falling anion gap, unrelated to saline use. The late phase was partly associated with lactate, related to surgery type, and early fluids appeared protective. There was a trend towards longer intensive care unit (+1.3 days) and hospital (+3.2 days) stay with metabolic acidosis. This is the first large study of the evolution of this common finding, demonstrating a pre-incision component. The early phase appears unavoidable or unpredictable, but the late phase might be modified by early fluid administration. It remains unclear whether acidosis of this type should be avoided.

Holistic assessment of women with hyperemesis gravidarum: A randomised controlled trial.

BACKGROUND: Hyperemesis gravidarum or severe nausea and vomiting of pregnancy affects women's physical, social and psychological wellbeing and often requires frequent hospital admissions. Current standard care may be too medically focussed to meet all of women's complex needs. AIM: The aim of this study is to test where using a validated questionnaire, the Hyperemesis Impact of Symptoms tool, delivered by a nurse to assess the overall effect of hyperemesis on an individual woman's life and to provide advice tailored to her specific needs, will help her cope better with her symptoms and reduce admissions to hospital. DESIGN: This study was a two arm randomised controlled trial in which women with hyperemesis from four hospitals were randomly allocated to one of two groups: (1) usual care and (2) usual care plus assessment with the Hyperemesis Impact of Symptoms questionnaire and a care plan tailored to their responses. PARTICIPANTS AND METHODS: Recruitment was from women who were admitted with hyperemesis gravidarum; diabetic women or those over 14 weeks gestation were excluded. Those who consented completed questionnaires to assess their quality of life and the severity of symptoms at baseline and at three time points over the following 6 weeks. RESULTS: Women's average social functioning, Hyperemesis Impact of Symptom scores and average number of admissions were not significantly different between either group. The average number of days in hospital for the questionnaire and tailored plan group was significantly lower, 4.97, compared with 6.14 in the usual care group. Using the questionnaire to plan individualised care was not associated with significant reduction in health care costs. CONCLUSION: Using the Hyperemesis Impact of Symptoms questionnaire to tailor a care plan to address women's individual needs was not associated with any significant improvements in the quality of life. The cost effectiveness analysis did not indicate that the questionnaire is cost saving. The Hyperemesis Impact of Symptoms questionnaire is a practical tool for nurses and midwives to assess the overall impact of hyperemesis gravidarum on the individual and could be useful for assessing symptoms and evaluating physical, social and psychological changes following treatment in either clinical or research settings.

Randomized clinical trial of fluid and salt restriction compared with a controlled liberal regimen in elective gastrointestinal surgery.

BACKGROUND: Excessive intravenous fluid prescription may play a causal role in postoperative complications following major gastrointestinal resectional surgery. The aim of this study was to investigate whether fluid and salt restriction would decrease postoperative complications compared with a more modern controlled liberal regimen. METHODS: In this observer-blinded single-site randomized clinical trial consecutive patients undergoing major gastrointestinal resectional surgery were randomized to receive either a liberal control fluid regimen or a restricted fluid and salt regimen. The primary outcome was postoperative complications of grade II and above (moderate to severe). RESULTS: Some 240 patients (194 colorectal resections and 46 oesophagogastric resections) were enrolled in the study; 121 patients were randomized to the restricted regimen and 119 to the control (liberal) regimen. During surgery the control group received a median (interquartile range) fluid volume of 2033 (1576-2500) ml and sodium input of 282 (213-339) mmol, compared with 1000 (690-1500) ml and 142 (93-218) mmol respectively in the restricted group. There was no significant difference in major complication rate between groups (38·0 and 39·0 per cent respectively). Median (range) hospital stay was 8 (3-101) days in the controls and 8 (range 3-76) days among those who received restricted fluids. There were four in-hospital deaths in the control group and two in the restricted group. Substantial differences in weight change, serum sodium, osmolality and urine : serum osmolality ratio were observed between the groups. CONCLUSION: There were no significant differences in major complication rates, length of stay and in-hospital deaths when fluid restriction was used compared with a more liberal regimen. REGISTRATION NUMBER: ISRCTN39295230 (http://www.controlled-trials.com).

Human adipose tissue from normal and tumoral breast regulaltes the behavior of mammary ephithelial cells

INTRODUCTION: Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. MATERIALS AND METHODS: Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. RESULTS: Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. CONCLUSIONS: We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact (AU)

The effect of inner tube placement on resistance and work of breathing through tracheostomy tubes: a bench test.

To reduce the risk of tracheostomy tube blockage, a removable inner tube can be used. However, this will reduce the size of the lumen and will increase airflow resistance and work of breathing. The magnitude of this increase in workload is unknown. We undertook a bench test to measure the effect. A lung model was developed to 'breathe' through the tracheostomy tube. We created pressure-volume curves from which we calculated work of breathing with and without an inner tube using 6-10 mm tracheostomy tubes over a range of respiratory rates and tidal volumes. The inner tube increased the resistive work of breathing by an average factor of 2.2. The extra work of breathing imposed easily exceeded the normal total work of breathing. Our results will aid a risk-benefit analysis when deciding whether to use inner tubes. Selecting a larger tracheostomy tube is likely to aid weaning from mechanical ventilation.

Assessing the performance of the Whisperflow continuous positive airway pressure generator: a bench study.

BACKGROUND: There are few data describing the performance of the Whisperflow continuous positive airway pressure (CPAP) generator. METHODS: (i) (a) A static test of 11 Whisperflow devices examining maximum flow generation with no load and with 2.5, 5, 7.5, 10, 15, and 20 cm H2O valve loading, at varying Fi(O2). (b) CPAP valves (Accu-peep(R), Vital Signs, Totowa, NJ, USA) were tested by measuring mean upstream pressure at varying flows in five valves (2.5, 5, 7.5, 10, 15, and 20 cm H2O). (ii) We measured the mean and minimum inspiratory mask pressure generated by a representative Whisperflow device in a model of spontaneous respiration. Measurements were made with combinations of Fi(O2), ventilatory frequency, tidal volume, and valve loading similar to those encountered in clinical practice. RESULTS: (i) (a) The flow generated by the Whisperflow valves decreases with increasing valve load and increasing Fi(O2) (from 140 to 20 litre min(-1)). (b) The CPAP valves maintain the required pressure within acceptable limits against varying flow. (ii) At all permutations, the mean inspiratory mask pressure was significantly lower than that required. At high inspiratory flow rates, the minimum inspiratory pressure approached atmospheric pressure. CONCLUSIONS: The Whisperflow may not perform as expected. Clinicians should be cautious when using this device, particularly with high Fi(O2) and CPAP valve load. The flow setting should be set at maximum. Failure of CPAP therapy may be due to failure of the generator. Further in vivo data are required.

Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort.

OBJECTIVE: Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial. DESIGN: We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 x TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45.5, range 18-80 years) were studied. RESULTS: Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%-71%) for TSH, 65% (58%-71%) for the fT4 x TSH product, 39% (20%-55%) for fT4 and 23% (3%-41%) for fT3. CONCLUSIONS: We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 x TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well-characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.

Integrated approaches to academic anaesthesia - the Cambridge experience.

There is mounting concern about the pressures experienced by University Departments of Anaesthesia, which, if lost, could threaten undergraduate peri-operative medicine teaching, development of critical appraisal skills among anaesthetists, and the future of coherent research programs. We have addressed these problems by establishing a foundation course in scientific methods and research techniques (the Cambridge SMART Course), complemented by competitive, fully funded, 12-month academic trainee attachments. Research conducted during academic attachments has been published and used to underpin substantive grant applications allowing work towards higher degrees. Following the attachment, a flexible scheme ensures safe reintroduction to clinical training. Research at consultant level is facilitated by encouraging applications for Clinician Scientist Fellowships, and by ensuring that the University Department champions, legitimises and validates the allocation of research time within the new consultant contract. We believe that these are important steps in safeguarding research and teaching in anaesthesia, critical care and peri-operative medicine.

Use of prone ventilation in neurogenic pulmonary oedema.

We present a case of neurogenic pulmonary oedema (NPO) due to subarachnoid haemorrhage that resulted in hypoxia refractory to conventional mechanical ventilation. Prone positioning was employed, resulting in rapid and sustained improvement in oxygenation. We discuss the pathogenesis of NPO and the mechanism of action of prone ventilation. Prone ventilation may be of value in the management of NPO, both in treating life-threatening hypoxia and in optimizing neurological recovery. Further data are required on its effect on intracranial pressure after subarachnoid haemorrhage.

Amniotic fluid embolism: a case report and review.

A 41-year old primigravida underwent caesarean section because of foetal distress following prostin induction of labour. Intraoperative coagulopathy, haemorrhage and hypotension necessitated a hysterectomy. Subsequently, she developed respiratory and renal failure, requiring mechanical ventilation and haemodialysis. She made a full recovery. The likely diagnosis was amniotic fluid embolism (AFE), a rare complication of pregnancy with a variable presentation, ranging from cardiac arrest and death through to mild degrees of organ system dysfunction with or without coagulopathy. The differential diagnosis includes pre-eclamptic toxaemia/pregnancy-induced hypertension, anaphylaxis and pulmonary embolism. There is no diagnostic test for AFE; the finding of foetal elements in the maternal circulation is non-specific. Historically, AFE was thought to induce cardiovascular collapse by mechanical obstruction of the pulmonary circulation. It is now thought that a combination of left ventricular dysfunction and acute lung injury occur, with activation of several of the clotting factors. An immunological basis for these effects is postulated. There is no specific therapy and treatment is supportive. The mortality of the condition remains high.