Explore the vast range of titles available.

Examine effects of dexmedetomidine on bladder urinary oxygen tension (PuO2) in critically ill patients and delineate mechanisms in an ovine model. In 12 critically ill patients: oxygen-sensing probe inserted in the bladder catheter and dexmedetomidine infusion at a mean (SD) rate of 0.9 ± 0.3 μg/kg/h for 24-h. In 9 sheep: implantation of flow probes around the renal and pulmonary arteries, and oxygen-sensing probes in the renal cortex, renal medulla and bladder catheter; dexmedetomidine infusion at 0.5 μg/kg/h for 4-h and 1.0 μg/kg/h for 4-h then 16 h observation. In patients, dexmedetomidine decreased bladder PuO2at 2 (−Δ11 (95% CI 7–16)mmHg), 8 (−Δ 7 (0.1–13)mmHg) and 24 h (−Δ 11 (0.4–21)mmHg). In sheep, dexmedetomidine at 1 μg/kg/h reduced renal medullary oxygenation (−Δ 19 (14–24)mmHg) and bladder PuO2 (−Δ 12 (7–17)mmHg). There was moderate correlation between renal medullary oxygenation and bladder PuO2; intraclass correlation co-efficient 0.59 (0.34–0.80). Reductions in renal medullary oxygenation were associated with reductions in blood pressure, cardiac output and renal blood flow (P < 0.01). Dexmedetomidine decreases PuO2in critically ill patients and in sheep. In sheep this reflects a decrease in renal medullary oxygenation, associated with reductions in cardiac output, blood pressure and renal blood flow. •Dexmedetomidine decreases bladder urinary oxygen tension in critically ill patients and in sheep•In sheep this reflects a decrease in renal medullary oxygenation•Dexmedetomidine induced reductions in renal medullary oxygenation are secondary to decreased cardiac output and renal blood flow

Prophylactic laxative regimens may prevent constipation but may increase diarrhea and subsequent rectal tube insertion. Our aim was to compare three prophylactic laxative regimens on the rate of rectal tube insertion (primary outcome) and major constipation- or diarrhea-associated complications. We conducted a cluster-crossover trial. Three pods in a single ICU were each randomized to one of three regimens for four months with rolling cross-over. All mechanically-ventilated and enterally-fed adult patients received either regimen: A) one coloxyl with senna BD from day one; B) two coloxyl with senna +20 ml lactulose BD commencing on day 3; or C) two coloxyl with senna tablets +20 ml lactulose BD commencing on day 6. We enrolled 570 patients (A = 170, B = 205, C = 195) with similar baseline features. Overall, 53 (9.3%) patients received a rectal tube, and insertion rate was not statistically different between the three regimens (A = 12.9%, B = 7.8%, C = 7.7%; p = 0.15). The proportions of patients with other major constipation- or diarrhea-associated complications were similar, as were major patient-centred outcomes. Earlier commencement of a prophylactic coloxyl-based laxative regimen (day 1 or 3) did not affect the rates of complications associated with constipation or diarrhea when compared to delayed introduction (day 6). •Prophylactic laxative regimens may increase diarrhea related complications.•This cluster-crossover randomized clinical trial compared 3 different regimens.•Prophylactic laxative regimens were commenced on day 1, 3 or 6 of enteral nutrition.•Earlier when compared to delayed introduction did not provide benefit.

Background Current guidelines for the provision of protein for critically ill patients are based on incomplete evidence, due to limited data from randomised controlled trials. The present pilot randomised controlled trial is part of a program of work to expand knowledge about the clinical effects of protein delivery to critically ill patients. The primary aim of this pilot study is to determine whether an enteral feeding protocol using a volume target, with additional protein supplementation, delivers a greater amount of protein and energy to mechanically ventilated critically ill patients than a standard nutrition protocol. The secondary aims are to evaluate the potential effects of this feeding strategy on muscle mass and other patient-centred outcomes. Methods This prospective, single-centred, pilot, randomised control trial will include 60 participants who are mechanically ventilated and can be enterally fed. Following informed consent, the participants receiving enteral nutrition in the intensive care unit (ICU) will be allocated using a randomisation algorithm in a 1:1 ratio to the intervention (high-protein daily volume-based feeding protocol, providing 25 kcal/kg and 1.5 g/kg protein) or standard care (hourly rate-based feeding protocol providing 25 kcal/kg and 1 g/kg protein). The co-primary outcomes are the average daily protein and energy delivered to the end of day 15 following randomisation. The secondary outcomes include change in quadriceps muscle layer thickness (QMLT) from baseline (prior to randomisation) to ICU discharge and other nutritional and patient-centred outcomes. Discussion This trial aims to examine whether a volume-based feeding protocol with supplemental protein increases protein and energy delivery. The potential effect of such increases on muscle mass loss will be explored. These outcomes will assist in formulating larger randomised control trials to assess mortality and morbidity. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: 12615000876594 UTN: U1111-1172-8563.

BackgroundImplantable brain–computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation.MethodsTwo participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks.ResultsUnsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%–100.00%) (trial mean (median, Q1–Q3)) at a rate of 13.81 (13.44, 10.96–16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%–100.00%) at 20.10 (17.73, 12.27–26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants.ConclusionWe describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.

PurposeThe effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation.MethodsThis is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO2) and the oxygen inspired fraction (FiO2). We explored the association between high PaO2 and FiO2 levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO2 and FiO2 levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury).ResultsThe analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO2 ranged from 93 to 166 mmHg. Exposure to higher PaO2 and FiO2 in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO2 and FiO2 levels, which remained independently associated with 6-month mortality.ConclusionsIn two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO2 and FiO2 varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO2 were due to use of higher FiO2 in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO2 and PaO2 are titrated to brain tissue oxygen monitoring (PbtO2) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.

PurposeTo investigate the impact of hydrocortisone treatment and illness severity on health-related quality of life (HRQoL) at 6 months in septic shock survivors from the ADRENAL trial.MethodsUsing the EuroQol questionnaire (EQ-5D-5L) at 6 months after randomization we assessed HRQoL in patient subgroups defined by hydrocortisone or placebo treatment, gender, illness severity (APACHE II < or ≥ 25), and severity of shock (baseline peak catecholamine doses < or ≥ 15 mcg/min). Additionally, in subgroups defined by post-randomisation variables; time to shock reversal (days), treatment with renal replacement therapy (RRT), and presence of bacteremia.ResultsAt 6 months, there were 2521 survivors. Of these 2151 patients (85.3%-1080 hydrocortisone and 1071 placebo) completed 6-month follow-up. Overall, at 6 months the mean EQ-5D-5L visual analogue scale (VAS) was 70.8, mean utility score 59.4. Between 15% and 30% of patients reported moderate to severe problems in any given HRQoL domain. There were no differences in any EQ-5D-5L domain in patients who received hydrocortisone vs. placebo, nor in the mean VAS (p = 0.6161), or mean utility score (p = 0.7611). In all patients combined, males experienced lower pain levels compared to females [p = 0.0002). Neither higher severity of illness or shock impacted reported HRQoL. In post-randomisation subgroups, longer time to shock reversal was associated with increased problems with mobility (p = < 0.0001]; self-care (p = 0.0.0142), usual activities (p = <0.0001] and pain (p = 0.0384). Amongst those treated with RRT, more patients reported increased problems with mobility (p = 0.0307) and usual activities (p = 0.0048) compared to those not treated. Bacteraemia was not associated with worse HRQoL in any domains of the EQ-5D-5L.ConclusionsApproximately one fifth of septic shock survivors report moderate to extreme problems in HRQoL domains at 6 months. Hydrocortisone treatment for septic shock was not associated with improved HRQoL at 6 months. Female gender was associated with worse pain at 6 months.

IntroductionCentral alveolar hypoventilation syndrome (CAHS) is a rare complication of stroke affecting the medullary respiratory centre. CAHS is characterised by impaired ventilatory response to CO2 leading to hypoventilation, hyper-capnoea and coma. Experimental studies have linked this syndrome to areas in the dorsal and ventrolateral medulla. CAHS is associated with long-term invasive ventilatory support, high mortality and morbidity. It is unclear whether sensitivity to CO2 can improve after the initial ischaemic medullary insult.CaseA 78 year old woman presenting with CAHS secondary to a unilateral left posterior inferior cerebellar artery infarction. MRI images confirmed that dorsal and ventrolateral medullary areas were affected. The patient was intubated initially for hyper-capnoeic respiratory failure and required a tracheostomy for ongoing respiratory support. To assess progress of respiratory recovery, we measured the patient’s ventilatory response to PaCO2 at 5, 7, and 14 days of admission. Parameters recorded included PaO2, ETCO2, PaCO2, pH, respiratory rate, and minute ventilation. During this time the patient underwent progressive periods of unsupported ventilation with close monitoring. Statistical correlation between respiratory rate and CO2 was measured by Pearson’s correlation coefficient (R). Her RR initially did not increase with PaCO2 during spontaneous ventilation (R=0.2604 p=0.077). Apnoeic episodes were frequent up to 41 episodes per 30 min of observation lasting up to 30 s. On day 7(R=0.7203 p<0.05) and up to day 14 (R=0.6295 p<0.05), there was a progressive statistically significant improvement in positive correlation between PCO2 and respiratory rate. This was associated with a reduction in apnoeic episodes possibly reflecting a recovery in ventilatory drive.ConclusionThis is the first detailed report demonstrating spontaneous recovery in CO2 responsiveness in the setting of CAHS secondary to unilateral medullary stroke. Plasticity of structures such as the retro-trapezoid nucleus are likely to play a role in recovery of CO2 sensitivity.References. Harper, et al. Functional neuroanatomy and sleep-disordered breathing: implications for autonomic regulation. Anatomical record2012;295(9):1385–95.. Mishina, et al. Efficacy of tracheostomy for central alveolar hypoventilation syndrome caused by lateral medullary infarction. Journal of Nippon Medical School2014;81(4):276–84.

Purpose To determine whether any of several quality improvement interventions with none specifically targeting methicillin-resistant Staphylococcus aureus (MRSA) were associated with a decline in endemic MRSA prevalence in an intensive care unit (ICU) where active screening and contact isolation precautions for known MRSA colonised patients are not practised. Setting Medical–surgical ICU with 2,000 admissions/year. Design 8.5-year retrospective time-series analysis. Interventions ICU re-location, antibiotic stewardship utilising computerised decision-support and infectious-diseases physician rounds, dedicated ICU infection control practitioners, alcohol-based hand rub solution (ABHRS). Method Regression modelling was used to evaluate trends in S. aureus prevalence density (monthly clinical isolates per 1,000 patient-days), antibiotic consumption, infection control consumables, ABHRS and their temporal relationship with MRSA prevalence. Results Methicillin-resistant S. aureus prevalence density decreased by 83% [95% confidence interval (CI) −68% to −91%, p  < 0.001]. Rates of MRSA bacteraemia decreased 89% (95% CI −79% to −94%, p  = 0.001) with no statistically significant change in methicillin-sensitive S. aureus bacteraemia. Hospital MRSA prevalence density decreased 17% (95% CI −5% to −27%, p  = 0.005), suggesting that ICU was not shifting MRSA elsewhere. In ICU, broad-spectrum antibiotic use decreased by 26% (95% CI −12% to −38%, p  = 0.008), coinciding with a decrease in MRSA, but time-series analysis did not show a significant association. On multivariate analysis, only ABHRS was significantly associated with a decrease in MRSA, but it was formally introduced late in the study period when MRSA was already in decline. Conclusion General quality improvement measures were associated with a decrease in endemic MRSA in a high-risk setting without use of resource-intensive active surveillance and isolation practices.