The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in traumaHayakawa, Mineji; Tagami, Takashi; Kudo, Daisuke; Ono, Kota; Aoki, Makoto; Endo, Akira; Yumoto, Tetsuya; Matsumura, Yosuke; Irino, Shiho; Sekine, Kazuhiko; Ushio, Noritaka; Ogura, Takayuki; Nachi, Sho; Irie, Yuhei; Hayakawa, Katsura; Ito, Yusuke; Okishio, Yuko; Muronoi, Tomohiro; Kosaki, Yoshinori; Ito, Kaori; Nakatsutsumi, Keita; Kondo, Yutaka; Ueda, Taichiro; Fukuma, Hiroshi; Saisaka, Yuichi; Tominaga, Naoki; Kurita, Takeo; Nakayama, Fumihiko; Shibata, Tomotaka; Kushimoto, Shigeki
doi: 10.1186/s40560-023-00682-3pmid: 37488591
BackgroundThe efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase.MethodsThis cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7–9 or 10–12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%.ResultsThe 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49–2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days.ConclusionsAlthough non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume.Trial registration number:umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.
Guideline-based management of acute respiratory failure and acute respiratory distress syndromeFujishima, Seitaro
doi: 10.1186/s40560-023-00658-3pmid: 36895001
Acute respiratory failure (ARF) is defined by acute and progressive hypoxemia caused by various cardiorespiratory or systemic diseases in previously healthy patients. Among ARF, acute respiratory distress syndrome (ARDS) is a serious condition with bilateral lung infiltration, which develops secondary to a variety of underlying conditions, diseases, or injuries. This review summarizes the current standard of care for ARF and ARDS based on current major guidelines in this field. When administering fluid in patients with ARF, particularly ARDS, restrictive strategies need to be considered in patients without shock or multiple organ dysfunction. Regarding oxygenation targets, avoiding excessive hyperoxemia and hypoxemia is probably a reasonable choice. As a result of the rapid spread and accumulation of evidence for high-flow nasal cannula oxygenation, it is now weakly recommended for the respiratory management of ARF in general and even for initial management of ARDS. Noninvasive positive pressure ventilation is also weakly recommended for the management of certain ARF conditions and as initial management of ARDS. Low tidal volume ventilation is now weakly recommended for all patients with ARF and strongly recommended for patients with ARDS. Limiting plateau pressure and high-level PEEP are weakly recommended for moderate-to-severe ARDS. Prone position ventilation with prolonged hours is weakly to strongly recommended for moderate-to-severe ARDS. In patients with COVID-19, ventilatory management is essentially the same as for ARF and ARDS, but awake prone positioning may be considered. In addition to standard care, treatment optimization and individualization, as well as the introduction of exploratory treatment, should be considered as appropriate. As a single pathogen, such as SARS-CoV-2, exhibits a wide variety of pathologies and lung dysfunction, ventilatory management for ARF and ARDS may be better tailored according to the respiratory physiologic status of individual patients rather than the causal or underlying diseases and conditions.
Lacosamide dosing in patients receiving continuous renal replacement therapyChaijamorn, Weerachai; Phunpon, Sathian; Sathienluckana, Thanompong; Charoensareerat, Taniya; Pattharachayakul, Sutthiporn; Rungkitwattanakul, Dhakrit; Srisawat, Nattachai
doi: 10.1186/s40560-023-00700-4pmid: 37946296
BackgroundLacosamide is one of the anticonvulsants used in critically ill patients. This study aimed to suggest appropriate lacosamide dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulations.MethodsMathematical models were created using published demographic and pharmacokinetics in adult critically ill patients. CRRT modalities with different effluent rates were added into the models. Lacosamide regimens were evaluated on the probability of target attainment (PTA) using pharmacodynamic targets of trough concentrations and area under the curve within a range of 5–10 mg/L and 80.25–143 and 143–231 mg*h/L for the initial 72 h-therapy, respectively. Optimal regimens were defined from regimens that yielded the highest PTA. Each dosing regimen was tested in a group of different 10,000 virtual patients.ResultsOur results revealed the optimal lacosamide dosing regimen of 300–450 mg/day is recommended for adult patients receiving both CRRT modalities with 20–25 effluent rates. The dose of 600 mg/day was suggested in higher effluent rate of 35 mL/kg/h. Moreover, a patient with body weight > 100 kg was less likely to attain the targets.ConclusionsVolume of distribution, total clearance, CRRT clearance and body weight were significantly contributed to lacosamide dosing. Clinical validation of the finding is strongly indicated.
Effect of a music intervention on anxiety in adult critically ill patients: a multicenter randomized clinical trialKakar, Ellaha; Ottens, Thomas; Stads, Susanne; Wesselius, Sanne; Gommers, Diederik A. M. P. J.; Jeekel, Johannes; van der Jagt, Mathieu
doi: 10.1186/s40560-023-00684-1pmid: 37592358
BackgroundPrevious studies show positive effect of music on reducing anxiety, pain, and medication requirement. Anxiety has become a more pertinent issue in the intensive care unit (ICU) since wakefulness is preferred according to recent guidelines. Nevertheless, evidence on the effect of music in ICU patients is scarce. Therefore, we studied the effect of music intervention on anxiety in ICU patients.MethodsA multicenter randomized clinical trial was conducted between August 2020 and December 2021 in ICU’s at an academic medical centre and two regional hospitals. Adult critically ill patients were eligible when hemodynamically stable and able to communicate (Richmond agitation-sedation scale (RASS) of at least − 2). Patients in the intervention arm were offered music twice daily during three days for at least 30 min per session. Patients in the control group received standard care. The primary outcome was anxiety level assessed with the visual analogue scale for anxiety [VAS-A; range 0–10] twice daily (morning and evening). Secondary outcomes included; 6-item state-trait anxiety inventory (STAI-6), sleep quality, delirium, heart rate, mean arterial pressure, pain, RASS, medication, ICU length of stay, patients’ memory and experience of ICU stay.Results94 patients were included in the primary analysis. Music did not significantly reduce anxiety (VAS-A in the intervention group; 2.5 (IQR 1.0–4.5), 1.8 (0.0–3.6), and 2.5 (0.0–3.6) on day 1, 2, and 3 vs. 3.0 (0.6–4.0), 1.5 (0.0–4.0), and 2.0 (0.0–4.0) in the control group; p > 0.92). Overall median daily VAS-A scores ranged from 1.5 to 3.0. Fewer patients required opioids (21 vs. 29, p = 0.03) and sleep quality was lower in the music group on study day one [5.0 (4.0–6.0) vs. 4.5 (3.0–5.0), p = 0.03]. Other outcomes were similar between groups.ConclusionsAnxiety levels in this ICU population were low, and music during 3 days did not decrease anxiety. This study indicates that efficacy of music is context and intervention-dependent, given previous evidence showing decreased anxiety.Trial registration Netherlands Trial Register: NL8595, Registered, 1 April 2020. ClinicalTrials.gov ID: NCT04796389, Registered retrospectively, 12 March 2021
Predictive value of soluble CD59 for poor 28-day neurological prognosis and all-cause mortality in patients after cardiopulmonary resuscitation: a prospective observatory studyWang, Ling; Li, Rui-Fang; Guan, Xiao-Lan; Liang, Shuang-Shuang; Gong, Ping
doi: 10.1186/s40560-023-00653-8pmid: 36732841
BackgroundsCD59, as a soluble form of CD59, is observed in multiple types of body fluids and correlated with the cell damage after ischemia/reperfusion injury. This study aims to observe the dynamic changes of serum sCD59 in patients after restoration of spontaneous circulation (ROSC) and explore the association of serum sCD59 with neurological prognosis and all-cause mortality in patients after ROSC.MethodsA total of 68 patients after ROSC were prospectively recruited and divided into survivors (n = 23) and non-survivors (n = 45) groups on the basis of 28-day survival. Twenty healthy volunteers were enrolled as controls. Serum sCD59 and other serum complement components, including sC5b-9, C5a, C3a, C3b, C1q, MBL, Bb, and pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), neurological damage biomarkers neuron-specific enolase (NSE) and soluble protein 100β (S100β) were measured by enzyme linked immunosorbent assay on day 1, 3, and 7 after ROSC. Neurologic outcome was assessed using cerebral performance category scores, with poor neurologic outcome defined as 3–5 points.ResultsIn the first week after ROSC, serum levels of sCD59, sC5b-9, C5a, C3a, C3b, C1q, MBL, Bb, TNF-α, IL-6, NSE and S100β were significantly elevated in patients after ROSC compared to healthy volunteers, with a significant elevation in the non-survivors compared to survivors except serum C1q and MBL. Serum sCD59 levels were positively correlated with serum sC5b-9, TNF-α, IL-6, NSE, S100β, SOFA score and APACHE II score. Moreover, serum sCD59 on day 1, 3, and 7 after ROSC could be used for predicting poor 28-day neurological prognosis and all-cause mortality. Serum sCD59 on day 3 had highest AUCs for predicting poor 28-day neurological prognosis [0.862 (95% CI 0.678–0.960)] and 28-day all-cause mortality [0.891 (95% CI 0.769–0.962)]. In multivariate logistic regression analysis, the serum level of sCD59D1 was independently associated with poor 28-day neurological prognosis and all-cause mortality.ConclusionsThe elevated serum level of sCD59 was positively correlated with disease severity after ROSC. Moreover, serum sCD59 could have good predictive values for the poor 28-day neurological prognosis and all-cause mortality in patients after ROSC.
An evaluation of the impact of the implementation of the Tele-ICU: a retrospective observational studyWatanabe, Taro; Ohsugi, Koichi; Suminaga, Yuri; Somei, Masayuki; Kikuyama, Kazuki; Mori, Maiko; Maruo, Hiroko; Kono, Nao; Kotani, Toru
doi: 10.1186/s40560-023-00657-4pmid: 36882878
BackgroundThe telemedicine intensive care unit (Tele-ICU) is defined as a system in which intensive care professionals remotely provide care to critically ill patients and support the on-site staff in the intensive care unit (ICU) using secured audio–video and electronic links. Although the Tele-ICU is expected to resolve the shortage of intensivists and reduce the regional disparities in intensive care resources, the efficacy has not yet been evaluated in Japan because of a lack of clinically available system.MethodsThis was a single-center, historical comparison study in which the impact of the Tele-ICU on ICU performance and changes in workload of the on-site staff were evaluated. The Tele-ICU system developed in the United States was used. Data for 893 adult ICU patients before the Tele-ICU implementation and for all adult patients registered in the Tele-ICU system from April 2018 to March 2020 were abstracted and included. We investigated ICU and hospital mortality and length of stay and ventilation duration after the Tele-ICU implementation in each ICU, and compared between pre and post implementation and changes over time. We also assessed physician workload as defined by the frequency and duration of access to the electronic medical record (EMR) of the targeted ICU patients.ResultsAfter the Tele-ICU implementation 5438 patients were included. In unadjusted data pre/post study showed significant decreases in ICU (8.5–3.8%) and hospital (12.4–7.7%) mortality and ICU length of stay (p < 0.001), and those values were maintained for 2 years. In data stratified by predicted hospital mortality, ICU and hospital actual mortality in high and medium risk patients decreased significantly after the implementation. Ventilation duration was shortened (p < 0.007). Access frequency of the on-site physicians decreased by 25%, and the decrease occurred in the daytime shift and in the physicians with 3–15 years of work experience.ConclusionsOur study showed the Tele-ICU implementation was associated with lower mortality, especially in medium and high risk patients, and decreased EMR-related tasks of on-site physicians. These results suggest that the Tele-ICU could be a solution of the shortage of intensivists and regional disparities for intensive care.