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institutional health service improvement projects as a key enabler to their success. CONCLUSIONS The study provides support that an intervention underpinned by challenge driven learning and team coaching can improve a range of health service delivery outcome variables.BACKGROUND The benefit of intravenous sodium bicarbonate administration in patients with severe metabolic acidosis remains controversial, partly due to lack of double-blind trials. From a practical viewpoint, such blinding requires testing of the stability of sodium bicarbonate in polyolefin bags. METHODS We examined seven samples of 100 mL 8.4% sodium bicarbonate diluted in 150 mL normal saline within a 250 mL polyolefin bag at time 0, 24 and 48 hours after preparation. We measured pH, Pco2, and bicarbonate concentration. RESULTS Over a period of 48 hours, both pH and Pco2 decreased significantly (hourly rate of change, -0.001 [P = 0.043) and -0.098 [P less then 0.001] respectively). However, the concentration of bicarbonate did not decrease, with an hourly rate of change of only -0.009 (P = 0.42). CONCLUSION When 100 mL of 8.4% sodium bicarbonate are diluted in 150 mL of normal saline within a 250 mL polyolefin bag, changes in pH and Pco2 over a 48-hour period are small and bicarbonate concentration remains stable.BACKGROUND Due to the lack of double-blind randomised controlled trials, the true effect of intravenous sodium bicarbonate therapy in ICU patients with metabolic acidosis remains unclear. METHODS We diluted 100 mL 8.4% sodium bicarbonate in 150 mL 5% dextrose (D5W) within a 250 mL polyolefin bag after removing 100 mL. We asked ICU clinicians to inspect a 250 mL bag containing sodium bicarbonate or a 250 mL bag where 100 mL of D5W had been removed and then returned. The bags were attached to intravenous giving sets. We asked participants to identify the contents of the bags. RESULTS Among 60 participants (39 nursing staff [65%], 20 medical staff [33.3%] and one pharmacist), 36 (60%) answered correctly. The Cohen κ for agreement between test bag content and participants' answers was 0.20 (95% CI, -0.05 to 0.45; P = 0.12), implying the answers were correct by chance. In the group of 28 participants who indicated they used a clue to help them decide their answer, 15 (53.6%) answered correctly, whereas in the remainder (n = 32), 21 (65.6%) answered correctly (P = 0.49). CONCLUSION When 100 mL of 8.4% sodium bicarbonate were diluted in 150 mL of D5W within a 250 mL polyolefin bag, clinicians were unable to correctly identify the contents of the bags. Our findings imply that sodium bicarbonate therapy can be successfully blinded.Inhaled nitric oxide has been used for 30 years to improve oxygenation and decrease pulmonary vascular resistance. Tofacitinib cost In the past 15 years, there has been increased understanding of the role of endogenous nitric oxide on cell surface receptors, mitochondria, and intracellular processes involving calcium and superoxide radicals. This has led to several animal and human experiments revealing a potential role for administered nitric oxide or nitric oxide donors in patients with systemic inflammatory response syndrome or ischaemia-reperfusion injury, and in patients for whom exposure of blood to artificial surfaces has occurred.BACKGROUND The best sedative medication to reduce delirium, mortality and long term brain dysfunction in mechanically ventilated septic patients is unclear. This multicentre, double-blind, randomised trial investigates the short term and long term effects of dexmedetomidine versus propofol for sedation in mechanically ventilated severely septic patients. OBJECTIVES To describe the statistical analysis plan for this randomised clinical trial comprehensively and place it in the public domain before unblinding. METHODS To ensure that analyses are not selectively reported, we developed a comprehensive statistical analysis plan before unblinding. This trial has an enrolment target of 420 severely septic and mechanically ventilated adult patients, randomly assigned to dexmedetomidine or propofol in a 11 ratio. Enrolment was completed in January 2019, and the study was estimated to be completed in September 2019. The primary endpoint is days alive without delirium or coma during first 14 study days. Secondary outcomes include 28-day ventilator-free days, 90-day all-cause mortality and cognitive function at 180 days. Time frames all begin on the day of randomisation. All analyses will be conducted on an intention-to-treat basis. CONCLUSION This study will compare the effects of two sedatives in mechanically ventilated severely septic patients. In keeping with the guidance on statistical principles for clinical trials, we have developed a comprehensive statistical analysis plan by which we will adhere, as this will avoid bias and support transparency and reproducibility. TRIAL REGISTRATION ClinicalTrials.gov (NCT01739933).OBJECTIVE Postprandial hypotension occurs frequently in older survivors of critical illness at 3 months after discharge. We aimed to determine whether postprandial hypotension and its predictors - gastric dysmotility and cardiovascular autonomic dysfunction - persist or resolve as older survivors of critical illness recover, and whether postprandial hypotension after intensive care unit (ICU) discharge is associated with adverse outcomes at 12 months. DESIGN Prospective observational study. SETTING Tertiary medical-surgical ICU. PARTICIPANTS Older adults (aged ≥ 65 years) who had been studied 3 months after ICU discharge and who returned for a follow-up study at 12 months after discharge. MAIN OUTCOME MEASURES On both occasions after fasting overnight, participants consumed a 300 mL drink containing 75 g glucose, radiolabelled with 20 MBq 99mTcphytate. Blood pressure, heart rate, blood glucose concentration and gastric emptying rate were measured concurrently before and after ingestion of the drink. Falls, quality of life, hospitalisation and mortality rates were also quantified. RESULTS Out of 35 older adults studied at 3 months, 22 returned for the follow-up study at 12 months. Postprandial hypotension was evident in 29% of participants (95% CI, 14-44%) at 3 months and 10% of participants (95% CI, 1-30%) at 12 months. Postprandial hypotension at 3 months was associated with a more than threefold increase in the risk of falls in the year after ICU discharge (relative risk, 3.7 [95% CI, 1.6-8.8]; P = 0.003). At 12 months, gastric emptying was normal (mean time taken for 50% of gastric contents to empty, 101.6 [SD, 33.3] min) and cardiovascular autonomic dysfunction prevalence was low (9% [95% CI, 1-29%]). CONCLUSIONS In older adults who were evaluated 3 and 12 months after ICU discharge, postprandial hypotension at 3 months was associated with an increased risk of subsequent falls, but the prevalence of postprandial hypotension decreased with time.
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