Objectives: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients. Design: A single-center, triple-blinded, randomized placebo-controlled trial. Setting: ICU of an academic hospital. Patients: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission. Interventions: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU. Measurements and Main Results: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings. Conclusions: Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly.

OBJECTIVES: The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. DESIGN: A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. SETTING: A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. PATIENTS: A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. MEASUREMENTS AND MAIN RESULTS: We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33–34°C) and those who received targeted temperature management at a higher target temperature (35–36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33–34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03–2.83] and 1.90 [95% CI, 1.15–3.16], respectively), but not in the patients of low or high severity (p_interaction = 0.033). Propensity score analysis also showed that targeted temperature management at 33–34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). CONCLUSIONS: Targeted temperature management at 33–34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35–40%, 35–40%, and 20% of the brain’s phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.

The aim of this study was to develop a scoring system for identifying the post-cardiac arrest syndrome (PCAS) patients with a good potential for recovery prior to the initiation of induced therapeutic hypothermia. A multi-center, retrospective, observational study was performed. Data of a total of 151 consecutive adults who underwent induced hypothermia after cardiac arrest (77 learning cases from two hospitals and 74 validation cases from two other hospitals) were analyzed. In the learning set, 8 factors (initial rhythm, witnessed status and time until return of spontaneous circulation, pH, serum lactate, motor score according to the Glasgow Coma Scale (GCS), gray matter attenuation to white matter attenuation ratio (GWR), serum albumin, and hemoglobin) were found to be strongly correlated with the neurological outcomes. A tentative scoring system was created from the learning data using these factors, and the predictive accuracy (sensitivity and specificity) was evaluated in terms of both internal validation (0.85 and 0.84) and external validation (cutoff 50%: 0.95 and 0.90, 30%: 0.87 and 0.98, 15%: 0.67 and 1.00). Finally, using all the data, we established a post-Cardiac Arrest Syndrome for induced Therapeutic hypothermia (CAST) score to predict the neurologic prognosis prior to initiation of induced hypothermia. The CAST score was developed to predict the neurological outcomes of PCAS patients treated by induced hypothermia. The likelihood of good recovery at 30 days was extremely low in PCAS patients with a CAST score of ≤15%. Prospective validation of the score is needed in the future.

There are numerous barriers to early mobilization (EM) in a resource-limited intensive care unit (ICU) without a specialized team or an EM culture, regarding patient stability while critically ill or in the presence of medical devices. We hypothesized that ICU physicians can overcome these barriers. The aim of this study was to investigate the safety of EM according to the Maebashi EM protocol conducted by ICU physicians. This was a single-center prospective observational study. All consecutive patients with an unplanned emergency admission were included in this study, according to the exclusion criteria. The observation period was from June 2015 to June 2016. Data regarding adverse events, medical devices in place during rehabilitation, protocol adherence, and rehabilitation outcomes were collected. The primary outcome was safety. A total of 232 consecutively enrolled patients underwent 587 rehabilitation sessions. Thirteen adverse events occurred (2.2%; 95% confidence interval, 1.2–3.8%) and no specific treatment was needed. There were no instances of dislodgement or obstruction of medical devices, tubes, or lines. The incidence of adverse events associated with mechanical ventilation or extracorporeal membrane oxygenation (ECMO) was 2.4 and 3.6%, respectively. Of 587 sessions, 387 (66%) sessions were performed at the active rehabilitation level, including sitting out of the bed, active transfer to a chair, standing, marching, and ambulating. ICU physicians attended over 95% of these active rehabilitation sessions. Of all patients, 143 (62%) got out of bed within 2 days (median 1.2 days; interquartile range 0.1–2.0). EM according to the Maebashi EM protocol conducted by ICU physicians, without a specialized team or EM culture, was performed at a level of safety similar to previous studies performed by specialized teams, even with medical devices in place, including mechanical ventilation or ECMO. Protocolized EM led by ICU physicians can be initiated in the acute phase of critical illness without serious adverse events requiring additional treatment.