The weekend effect in status epilepticus: a national cohort study.

Higher mortality following admission to hospital at the weekend has been reported for several conditions. It is unclear whether this variation is due to differences in patients or their care. Status epilepticus mandates hospital admission and usually critical care: its study might provide new insights into the nature of any weekend effect. We studied 20,922 adults admitted to UK critical care with status epilepticus from 2010 to 2015. We used multiple logistic regression to evaluate the association between weekend admission and in-hospital mortality, comparing university hospitals with other hospitals. There were 2462 in-hospital deaths (12%). There was no difference in mortality after weekend admission to university hospitals, adjusted odds ratio (95%CI) 0.99 (0.84-1.16), p = 0.89. Mortality was less after weekend admission than after admissions Monday to Friday in hospitals not associated with a university, adjusted odds ratio (95%CI) 0.74 (0.64-0.87), p = 0.0001. There is no evidence that adults admitted to UK critical care at the weekend in status epilepticus are more likely to die than similar patients admitted during the week.

Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro.

PURPOSE: Neutrophil Extracellular Traps (NETs) are extracellular neutrophil derived DNA webs which have been implicated in cancer progression and in the development of metastases. NETs production in patients with colorectal cancer was investigated to elucidate their role and prognostic significance. METHODS: Systemic neutrophils were isolated from consecutive patients with colorectal cancer and from age-matched healthy volunteers. Neutrophils were stimulated to produce NETs which were quantified by a measure of the fluorescence of the extracellular DNA. The impact of cancer location, tumour stage, and patient outcomes (complications, length of stay, and mortality) on NET production was investigated. RESULTS: Quantification of NET formation was performed in patients with colorectal cancer (n = 45) and in well-matched healthy individuals (n = 20). Significant increases in NETs production in response to no stimulant (9,735 AFU versus 11347 AFU, p = 0.0209), IL-8 (8,644 AFU versus 11,915 AFU, p = 0.0032), and LPS (10,576 AFU versus 12,473 AFU, p = 0.0428) were identified in patients with colorectal cancer. A significant increase in NETs production in response to fMLP was detected in patients who developed significant postoperative complications (11,760 AFU versus 18,340 AFU, p = 0.0242) and who had a prolonged hospital recovery (9,008 AFU versus 12,530 AFU, p = 0.0476). An increase in NETs production was also observed in patients who died, but this did not reach statistical significance. Cancer location and tumour stage did not appear to affect preoperative NETs production. CONCLUSIONS: Patients with colorectal cancer have significantly increased NETs production in vitro when compared to healthy volunteers, possibly implicating them in cancer development. Adverse patient outcomes were associated with increased preoperative NETs production, which highlights them as potential therapeutic targets.

Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care patients and lacks effective treatments. A previous randomised controlled Phase II trial suggested that an intravenous (i.v.) infusion of salbutamol may be beneficial, as it reduced extravascular lung water and plateau airway pressure. The Beta-Agonist Lung injury TrIal-2 (BALTI-2) was initiated to evaluate the effects of this intervention on mortality in patients with ARDS. OBJECTIVES: To evaluate whether or not, in patients with ARDS, an i.v. infusion of salbutamol given at 15 µg/kg ideal body weight (IBW)/hour for up to 7 days, compared with a placebo (0.9% sodium chloride) infusion, reduces 28-day all-cause mortality and other clinical outcomes. To evaluate salbutamol's clinical effectiveness and its cost-effectiveness in subgroups of patients. DESIGN: A multicentre, randomised, placebo-controlled trial. SETTING: Forty-six intensive care units (ICUs) in the UK. PARTICIPANTS: Patients were eligible if they (1) were intubated and mechanically ventilated patients in participating ICUs; (2) were within 72 hours of onset of ARDS; (3) fulfilled American-European Consensus Conference definition for ARDS {acute-onset, severe hypoxaemic respiratory failure [partial pressure of oxygen in arterial blood/fraction of inspired oxygen ≤ 26.7 kPa (200 mmHg)] and bilateral infiltrates on the chest radiograph in the absence of clinical evidence of left atrial hypertension}; and (4) were aged ≥ 16 years. INTERVENTIONS: Intravenous infusion of salbutamol (15 µg/kg IBW/hour) or placebo (0.9% saline) for up to 7 days. MAIN OUTCOME MEASURES: All-cause mortality 28 days after randomisation, mortality at (first) discharge from ICU, mortality at (first) discharge from hospital, number of ventilator-free days, number of organ failure-free days, mortality at 12 months post randomisation, side effects (tachycardia/new arrhythmia/lactic acidosis) sufficient to stop treatment with trial drug, health-related quality of life (European Quality of Life-5 Dimensions and Short Form questionnaire-12 items at 6 and 12 months after randomisation), length of stay in critical care unit and length of stay in hospital. RESULTS: Forty-six ICUs recruited patients to the trial. A total of 326 patients were randomised; 162 were allocated to salbutamol and 164 to placebo. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality: 55 (34%) of 161 patients died in the salbutamol group compared with 38 (23%) of 163 in the placebo group (risk ratio 1.47, 95% confidence interval 1.03 to 2.08). CONCLUSIONS: Treatment with i.v. salbutamol early in the course of ARDS was poorly tolerated, is unlikely to be beneficial and could worsen outcomes. Further trials of ß-agonists in patients with ARDS are unlikely to be conducted. Some questions remain, such as whether or not there may be benefit at a different dose or in specific populations, but any studies investigating these would require a very strong rationale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38366450. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Prediction by computerised tomography of distance from skin to epidural space during thoracic epidural insertion.

In this single group observational study on 29 patients, we describe a technique that predicts the depth of the epidural space, calculated from the routine pre-operative chest computerised tomography (CT) scan using Pythagorean triangle trigonometry. We also compared the CT-derived depth of the epidural space with the actual depth of needle insertion. The CT-derived and the actual depths of the epidural space were highly correlated (r = 0.88, R2 = 0.78, p < 0.0001). The mean (95% CI) difference between CT-derived and actual depths was 0.26 (0.03-0.49) cm. Thus, the CT-derived depth tends to be greater than the actual depth by between 0.03 and 0.49 cm. There were no associations between either the CT-derived or the actual depth of the epidural space and age, weight, height or body mass index.

The effects of remifentanil on haemodynamic stability during rigid bronchoscopy.

We examined the effect of remifentanil on the haemodynamic response to rigid bronchoscopy in 22 adult ASA 2-4 patients, randomly allocated to receive 1.0 microg.kg-1 remifentanil over 1 min followed by 0.5 microg.kg-1.min-1 (remifentanil group) or 2.0 microg.kg-1 fentanyl followed by a saline infusion (control group). Following the initial infusion, all patients received a sleep dose of propofol followed by rocuronium 0.6 mg.kg-1 and their lungs were ventilated using a Sander's injector attached to the rigid bronchoscope. Direct arterial blood pressures, heart rate and ST segment changes on the CM5 lead configuration of the electrocardiograph were measured at 1-min intervals from before induction of anaesthesia until the end of bronchoscopy. Arterial pressures and heart rate were similar in the two groups before and after induction of anaesthesia. Remifentanil attenuated the haemodynamic response to bronchoscopy (p < 0.05 for increases in arterial pressures and heart rate). Four patients in the remifentanil group had ST segment depression compared with eight patients in the control group, but this was not statistically significant.