The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial.

OBJECTIVES: To test the hypothesis that nurse led follow-up programmes are effective and cost effective in improving quality of life after discharge from intensive care. DESIGN: A pragmatic, non-blinded, multicentre, randomised controlled trial. SETTING: Three UK hospitals (two teaching hospitals and one district general hospital). PARTICIPANTS: 286 patients aged >or=18 years were recruited after discharge from intensive care between September 2006 and October 2007. INTERVENTION: Nurse led intensive care follow-up programmes versus standard care. Main outcome measure(s) Health related quality of life (measured with the SF-36 questionnaire) at 12 months after randomisation. A cost effectiveness analysis was also performed. RESULTS: 286 patients were recruited and 192 completed one year follow-up. At 12 months, there was no evidence of a difference in the SF-36 physical component score (mean 42.0 (SD 10.6) v 40.8 (SD 11.9), effect size 1.1 (95% CI -1.9 to 4.2), P=0.46) or the SF-36 mental component score (effect size 0.4 (-3.0 to 3.7), P=0.83). There were no statistically significant differences in secondary outcomes or subgroup analyses. Follow-up programmes were significantly more costly than standard care and are unlikely to be considered cost effective. CONCLUSIONS: A nurse led intensive care follow-up programme showed no evidence of being effective or cost effective in improving patients' quality of life in the year after discharge from intensive care. Further work should focus on the roles of early physical rehabilitation, delirium, cognitive dysfunction, and relatives in recovery from critical illness. Intensive care units should review their follow-up programmes in light of these results. TRIAL REGISTRATION: ISRCTN 24294750.

A prospective observational study of ICU patient position and frequency of turning.

Positioning and turning critically ill patients may be beneficial but there are little data on current practice. We prospectively recorded patient position every hour over two separate days in 40 British intensive care units and analysed 393 sets of observation. Five patients were prone at any time and 3.8% (day 1) and 5% (day 2) were on rotating beds. Patients were on their back for 46.1% of observations, turned left for 28.4% and right for 25.5%, and head up for 97.4%. A turn was defined as a change between on back, turned left or turned right. The average time (SD) between turns was 4.85 (3.3) h. There was no significant association between the average time between turns and age, weight, height, gender, respiratory diagnosis, intubated and ventilated, sedation score, day of week or nurse:patient ratio. There was a significant difference between hospitals in the frequency with which patients were turned.

Ethics and law in the intensive care unit.

Intensive Care Medicine epitomises the difficulties inherent in modern medicine. In this chapter we examine some key medicolegal and ethical areas that are evolving. The principles of autonomy and consent are well established, but developments in UK caselaw have shown that the courts may be moving away from their traditional deference of the medical profession. We examine some recent cases and discuss the impact that these cases may have on practice in Intensive Care.

Posterior spinal ligament rupture associated with laryngeal mask insertion in a patient with undisclosed unstable cervical spine.

A case of posterior spinal ligament rupture associated with a general anaesthetic for a laparoscopic cholecystectomy is reported. The role of the general anaesthetic in this case is discussed and a review of the literature is presented.

Transforming growth factor-beta1 in autoimmune hepatitis: correlation of liver tissue expression and serum levels with disease activity.

BACKGROUND/AIMS: Transforming growth factor-beta1 (TGF-beta1) is considered the most important mediator of hepatic fibrogenesis. At the same time, TGF-beta1 is an immunosuppressive cytokine. Development of fibrosis, often rapid, is a characteristic of autoimmune hepatitis, as is spontaneous systemic immunosuppression. The aim of our study was therefore to define the role of TGF-beta1 in autoimmune hepatitis. METHODS/RESULTS: Using the MV 1Lu bioassay, we found markedly elevated serum levels of TGF-beta1 (median 109 ng/ml) in active autoimmune hepatitis, which normalised when patients reached biochemical remission following immunosuppressive therapy (median 34 ng/ml; p=0.0001 compared to active disease). With a newly established ELISPOT-assay for TGF-beta1-producing cells, we could exclude an increase in TGF-beta1-producing peripheral blood cells as a source of the elevated TGF-beta1. However, by in situ hybridisation and immunohistochemistry, we found strong TGF-beta1 expression in the inflamed liver. In addition to non-parenchymal and infiltrating cells, many hepatocytes showed strong staining for TGF-beta1. TGF-beta1 expression in the liver normalised in remission, yet was still somewhat increased in patients with biochemical remission but remaining histological disease activity. CONCLUSIONS: These results suggest that TGF-beta1 is an important mediator in active autoimmune hepatitis. They support the theory that immunosuppressive therapy needs to be guided by histology, as prevention of the development of cirrhosis presumably requires near complete suppression of TGF-beta1 in the liver; this is only found when there is no longer any histological evidence of inflammation.

Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.

BACKGROUND & AIMS: Inflammatory liver disease as well as rejection of liver allografts are thought to be mediated by resident antigen-presenting cells in the liver. At the same time, in vivo antigen presentation in the liver appears to be a more tolerogenic than systemic antigen challenge. The aim of this study was to show and characterize the antigen-presenting capability of sinusoidal endothelial cells and Kupffer cells. METHODS: Purified murine sinusoidal endothelial cells and Kupffer cells were studied for their ability to serve as accessory cells and antigen-presenting cells by proliferation assays. They were also studied for their expression of interleukin 1 and the B7 costimulatory molecules by Northern blotting, polymerase chain reaction, and flow cytometry. RESULTS: Both cell types expressed interleukin 1 messenger RNA and could serve equally well as accessory and antigen-presenting cells. B7-2 messenger RNA and surface expression on sinusoidal endothelial cells and on Kupffer cells was shown. Antibodies to the B7 molecules inhibited antigen presentation. Addition of interleukin 10 as a regulatory cytokine secreted by Kupffer cells was suppressive. CONCLUSIONS: Sinusoidal endothelial cells carry functional B7-2 molecules and can serve as effective antigen-presenting cells. However, antigen presentation by sinusoidal endothelial cells may be locally down-regulated by interleukin 10.

Skin tethering after dilatational percutaneous tracheostomy.

Percutaneous tracheostomy is increasingly preferred for patients in the Intensive Care Unit. It is a convenient method with a low incidence of complications. Skin tethering has not previously been emphasized as a complication of this technique and, although primarily cosmetic, may result in significant morbidity.

Cytochrome oxidase activity reveals parcellations of the pigeon's ectostriatum.

The endogenous cytochrome oxidase activity of the pigeon's ectostriatum, the primary telencephalic structure of the tectofugal visual pathway, was histochemically demonstrated and a heterogeneous distribution of the reaction product was observed. In cross-sections the medial, central and ventrolateral parts of the ectostriatum showed high levels of activity while the centroventral and dorsolateral ectostriatum remained weakly labelled. Only slight left-right and interindividual variations were found in the pattern of labelling. These data demonstrate for the first time anatomical subdivisions within the ectostriatal core and open the possibility of functional parcellations within this structure.

The use of pulmonary artery catheters in intensive care: time for reappraisal?

The precise role of the pulmonary artery catheter (PAC) in reducing the morbidity and mortality of intensive care patients remains uncertain. Future studies of the different patient groups who possibly benefit from their use may well require multicentre trials in order to include sufficient numbers and produce significant conclusions. This would suggest a need for a consensus opinion on how PACs are actually used to obtain the different physiological variables which can influence patient management. A questionnaire was designed to assess the degree of conformity of PAC use in intensive care; the questions were derived from a Medline search and considered by the authors to represent a cross-section of the different aspects and potential errors of PAC use. A postal questionnaire was sent from a District General Hospital to 42 adult Intensive Care Units (ICUs) requesting information on the use of PACs in each ICU. The reply rate was 93%, with all but one of the respondents using PACs. The questionnaire obtained information in different areas of PAC use: 1. General usage of PACs. 2. Measurement of patient height and weight. 3. Confirmation of position of PAC tip. 4. Measurement of pulmonary artery wedge pressure (PAWP). 5. Measurement of cardiac output (CO). 6. Derived values. 7. Monitoring for PAC-related sepsis. The results of the questionnaire demonstrated a considerable lack of standardisation in the use of PACs in the United Kingdom.(ABSTRACT TRUNCATED AT 250 WORDS)

The dopaminergic innervation of the pigeon caudolateral forebrain: immunocytochemical evidence for a 'prefrontal cortex' in birds?

The dopaminergic (DA) innervation of the caudal telencephalon of the pigeon was investigated with an antiserum against glutaraldehyde-conjugated dopamine. It was found that the DA-like fibers were distributed within the Paleostriatum augmentatum and the dorsal Archistriatum in a dense meshwork of fibers, while most of the remaining part of the caudal forebrain was innervated by dopaminergic axons which were coiled up like baskets around unlabelled neurons. Within the basket-type innervated structures, the Neostriatum caudolaterale (Ncl) could be distinguished by the high density of its dopaminergic fibers. Retrograde tracer injections into Ncl revealed afferents from the Area ventralis tegmentalis (AVT) and the n. tegmenti pedunculo-pontinus pars compacta (TPc). Since large numbers of DA-like perikarya could be detected in AVT and TPc, it is supposed that these two structures constitute the main source of the dopaminergic innervation of the Ncl. Previous studies had suggested that the Ncl represents an avian equivalent to the mammalian prefrontal cortex. The present results reveal an organization similar to that of the mesocortico-prefrontal system and would thus strengthen this hypothesis.

Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports.

OBJECTIVE: To examine the possible contribution of sedation with propofol in the deaths of children who were intubated and required intensive care. DESIGN: Case note review. SETTING: Three intensive care units. SUBJECTS: Five children with upper respiratory tract infections aged between 4 weeks and 6 years. RESULTS: Four patients had laryngotracheo-bronchitis and one had bronchiolitis. All were sedated with propofol. The clinical course in all five cases was remarkably similar: an increasing metabolic acidosis was associated with brady-arrhythmia and progressive myocardial failure, which did not respond to resuscitative measures. All children developed lipaemic serum after starting propofol. These features are not usually associated with respiratory tract infections. No evidence was found of viral myocarditis, which was considered as a possible cause of death. CONCLUSION: Although the exact cause of death in these children could not be defined, propofol may have been a contributing factor.