Analysis of sleep spindles shows that dexmedetomidine produces a state closely resembling physiological S2 sleep in humans, which gives further support to earlier experimental evidence for activation of normal non-rapid eye movement sleep-promoting pathways by this sedative agent.

IntroductionDeep sedation is associated with adverse patient outcomes. We recently described a novel sedation-monitoring technology, the Responsiveness Index (RI), which quantifies patient arousal using processed frontal facial EMG data. We explored the potential effectiveness and safety of continuous RI monitoring during early intensive care unit (ICU) care as a nurse decision-support tool.MethodsIn a parallel-group controlled single centre proof of concept trial, patients requiring mechanical ventilation and sedation were randomized via sequential sealed envelopes following ICU admission. Control group patients received hourly clinical sedation assessment and daily sedation holds; the RI monitor was connected but data were concealed from clinical staff. The intervention group received control group care, but RI monitoring was visible and nurses were asked to adjust sedation to maintain patients with an RI>20 whenever possible. Traffic-light colour coding (RI<20, Red; 20–40, Amber; >40, Green) simplified decision-making. The intervention lasted up to 48 hours. Sixteen nurses were interviewed to explore their views of the novel technology.ResultsWe analysed 74 patients treated per protocol (36 intervention; 38 control). The proportion of patients with RI<20 was identical at the start of monitoring (54 % both groups). Overall, the proportion of time with RI<20 trended to lower values for the intervention group (median 16 % (1–3rd quartile 8–30 %) versus 33 % (10–54 %); P = 0.08); sedation and analgesic use was similar. A post hoc analysis restricted to patients with RI<20 when monitoring started, found intervention patients spent less time with low RI value (16 % (11–45 %) versus 51 % (33–72 %); P = 0.02), cumulative propofol use trended to lower values (median 1090 mg versus 2390 mg; P = 0.14), and cumulative alfentanil use was lower (21.2 mg versus 32.3 mg; P = 0.01). RASS scores were similar for both groups. Sedation related adverse event rates were similar (7/36 versus 5/38). Similar proportions of patients had sedation holds (83 % versus 87 %) and were extubated (47 % versus 44 %) during the intervention period. Nurses valued the objective visible data trends and simple colour prompts, and found RI monitoring a useful adjunct to existing practice.ConclusionsRI monitoring was safe and acceptable. Data suggested potential to modify sedation decision-making. Larger trials are justified to explore effects on patient-centred outcomes.Trial registrationNCT01361230 (registered April 19, 2010)Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1043-1) contains supplementary material, which is available to authorized users.

Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (P K ) of 50% spectral edge frequency 5 0.23, standard error (SE) 5 0.03; P K of delta power 5 0.76, SE 5 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (P K 5 0.88, SE 5 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval 5 0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes.

Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. Acknowledgement The study was funded by the 'One Hundred People' project of Shanghai Sanitary Bureau (03-77-20). Introduction Although extrapulmonary ALI/ARDS is a common clinical entity, most animal models used to study this disease are induced by direct lung injuries. Our intention was therefore to investigate whether a condition resembling ALI/ARDS develops during the course of a fecal peritonitis in pigs; in that case experimental peritonitis would also prove as a clinically relevant ARDS model. Methods In 10 anesthetized, mechanically ventilated, and instrumented pigs fecal peritonitis was induced by inoculating autologue feces pellets suspended in saline. Mechanical ventilation was set with VT = 8 ml/kg, FiO 2 to reach a SaO 2 target of >90%, PEEP = 10 cmH 2 O if PaO 2 /FiO 2 > 300 and 12 cmH 2 O if PaO 2 /FiO 2 < 300, and respiratory rate to obtain a PaCO 2 of 35-45 mmHg. Before as well as 12 and 24 hours after peritonitis induction we measured the PaO 2 /FiO 2 ratio, the total compliance of the respiratory system (C), calculated as VT/(P plateau -PEEP) and inspiratory airway resistance (R i ) calculated as (P max -P plateau ) / mean inspiratory flow. Data are mean [range]. Results For data see Table 1. During the course of the 24-hour study period, six of 10 animals developed gas exchange deteriorations consistent w...

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