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In recent decades, several databases of critically ill patients have become available in both low-, middle-, and high-income countries from all continents. These databases are also rich sources of data for the surveillance of emerging diseases, intensive care unit performance evaluation and benchmarking, quality improvement projects and clinical research. The Epimed Monitor database is turning 15 years old in 2024 and has become one of the largest of these databases. In recent years, there has been rapid geographical expansion, an increase in the number of participating intensive care units and hospitals, and the addition of several new variables and scores, allowing a more complete characterization of patients to facilitate multicenter clinical studies. As of December 2023, the database was being used regularly for 23,852 beds in 1,723 intensive care units and 763 hospitals from ten countries, totaling more than 5.6 million admissions. In addition, critical care societies have adopted the system and its database to establish national registries and international collaborations. In the present review, we provide an updated description of the database; report experiences of its use in critical care for quality improvement initiatives, national registries and clinical research; and explore other potential future perspectives and developments.

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Background & Aims: Precise assessment of postoperative volume status is important to administrate optimal fluid management. Bioelectrical impedance analysis (BIA) which measures the body composition using electric character. Extracellular water (ECW) ratio by BIA represented as the ratio of ECW to total body water (TBW) and is known to reflect the hydration status. Based on this, we aimed to determine whether aggressive fluid control using ECW ratio could improve clinical outcomes through a single blind, randomized controlled trial., Methods: From November 2021 to December 2022, intensive care unit (ICU) patients admitted after surgery were randomly assigned to an intervention group or a control group whether postoperative fluid management was controlled via BIA. Among patients in the intervention group, dehydrated patients received a bolus infusion with crystalloid fluid whereas diuretics were administrated to overhydrated patients until the value of ECW ratio fell within its normal setting range (0.390-0.406). Contrarily, BIA was performed once a day for the control group. Patients in the control group received traditional fluid treatment regardless of BIA results. Primary outcome was in-hospital mortality in two groups. The secondary outcomes were postoperative morbidities, 28-day mortality., Results: 77 patients of the intervention group and 90 patients of the control group were finally analyzed. The in-hospital mortality (0 in intervention, 4.4% in control, p = 0.125) and 28-day mortality (1.3% in intervention, 14.4% in control, p = 0.002) showed lower incidence in the intervention group than in the control group. In multivariate analysis, the overhydrated status whose ECW ratio exceeding 0.406 [odds ratio (OR): 2.731, 95% confidence interval (CI): 1.001-7.663, p = 0.049] and high capillary leak index (CLI) value at ICU admission (OR: 1.024, 95% CI: 1.008-1.039, p = 0.002) were risk factors of postoperative morbidities. Regarding the 28-day mortality, high CLI value (OR: 1.025, 95% CI: 1.002-1.050, p = 0.037) and traditional strategy without BIA monitoring (OR: 9.903, 95% CI: 1.095-89.566, p = 0.041) were the significant predisposing factors., Conclusion: Our results revealed the rigorous fluid treatment with volume control based on ECW ratio by BIA failed to achieve significant improvement in in-hospital mortality, but it could reduce 28-day mortality of ICU patients. Monitoring of ECW ratio may help establish optimal fluid treatment strategies for postoperative ICU patients who are susceptible to fluid imbalances with fluid overload., Trial Registration: ClinicalTrials.gov, NCT06097923, retrospectively registered on October 16, 2023, https://clinicaltrials.gov/study/NCT06097923?term=NCT06097923&rank=1., Competing Interests: Conflict of interest The authors declare that there are no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This tutorial discusses a methodology for causal inference using longitudinal modified treatment policies. This method facilitates the mathematical formalization, identification, and estimation of many novel parameters and mathematically generalizes many commonly used parameters, such as the average treatment effect. Longitudinal modified treatment policies apply to a wide variety of exposures, including binary, multivariate, and continuous, and can accommodate time-varying treatments and confounders, competing risks, loss to follow-up, as well as survival, binary, or continuous outcomes. Longitudinal modified treatment policies can be seen as an extension of static and dynamic interventions to involve the natural value of treatment and, like dynamic interventions, can be used to define alternative estimands with a positivity assumption that is more likely to be satisfied than estimands corresponding to static interventions. This tutorial aims to illustrate several practical uses of the longitudinal modified treatment policy methodology, including describing different estimation strategies and their corresponding advantages and disadvantages. We provide numerous examples of types of research questions that can be answered using longitudinal modified treatment policies. We go into more depth with one of these examples, specifically, estimating the effect of delaying intubation on critically ill COVID-19 patients' mortality. We demonstrate the use of the open-source R package lmtp to estimate the effects, and we provide code on https://github.com/kathoffman/lmtp-tutorial., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: The most adequate amount of protein that should be administered to critically ill patients is still debated and diverging findings are recently accumulating. We hypothesized that the effect of protein administration might depend on the amount of muscle mass., Methods: A secondary analysis of a single-centre prospective observational study of body composition in critically ill patients. Mechanically-ventilated subjects with an expected intensive care unit (ICU) stay >72 h were enrolled. Within 24 h from ICU admission, bioimpedance-derived muscle mass (BIA MM) and rectus femoris cross-sectional area (RF CSA) were measured. The amount of proteins and calories administered on the 7th ICU day was recorded., Results: We enrolled 94 subjects (65 males, actual body weight 72.9 ± 14.4 Kg, BMI 26.0 ± 4.8 kg/m 2 ). Actual body weight was only weakly related to BIA MM (R = 0.478, p < 0.001) and not related to RF CSA (R = 0.114, p = 0.276). A higher protein intake was associated with a reduced mortality in the highest quartile of BIA MM (OR 0.68 [0.46; 0.99] per each 10 g of proteins administered) and in the third (OR 0.74 [0.57; 0.98]) and highest quartile of RF CSA (OR 0.68 [0.48; 0.96])., Conclusion: A higher protein intake was associated with lower ICU mortality only in patients admitted with a higher muscle mass, as either assessed by BIA or muscle ultrasound., Competing Interests: Conflict of interest MU reports receiving speaking and lecture fees from Nestle HealthCare Nutrition Inc, Fresenius Kabi AB and Baxter International Inc. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Prehospital blood gas analysis (BGA) is an evolving field that offers the potential for early identification and management of critically ill patients. However, the utility and accuracy of prehospital BGA are subjects of ongoing debate., Objectives: We aimed to provide a comprehensive summary of the current literature on prehospital BGA, including its indications, methods, and feasibility., Methods: We performed a scoping review of prehospital BGA. A thorough search of the PubMed, Embase, and Web of Science databases was conducted to identify relevant studies focusing on prehospital BGA in adult patients., Results: Fifteen studies met the inclusion criteria. Prehospital BGA was most frequently performed in patients in out-of-hospital cardiac arrest, followed by traumatic and nontraumatic cases. The parameters most commonly analyzed were pH, pCO 2 , pO 2 , and lactate. Various sampling methods, including arterial, venous, and intraosseous, were reported for prehospital BGA. While prehospital BGA shows promise in facilitating early identification of critical patients and guiding resuscitation efforts, logistical challenges are to be considered. The handling of preclinical BGA is described as feasible and useful in most of the included studies., Conclusion: Prehospital BGA holds significant potential for enhancing patient care in the prehospital setting, though technical challenges need to be considered. However, further research is required to establish optimal indications and demonstrate the benefits for prehospital BGA in specific clinical contexts., Competing Interests: Declaration of competing interest GP is author of an included study and was not involved in study selection. For the remaining authors, none were declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Background and Objectives: Gastric tube feeding and postpyloric tube feeding are two common forms of enteral nutrition in critically ill patients. This study aimed to compare the efficacy and safety of gastric tube feeding with that of postpyloric tube feeding in critically ill patients., Methods and Study Design: PubMed, Embase, and Cochrane Library were systematically searched for eligible trials from their inception until March 2023. Relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to estimate categorical and continuous outcomes using the random-effects model., Results: Sixteen trials involving 1,329 critically ill patients were selected for the final meta-analysis. Overall, we noted that gastric tube feeding showed no significant difference from post-pyloric tube feeding in mortality (p = 0.891), whereas the risk of pneumonia was significantly increased in patients who received gastric tube feeding (RR: 1.45; p = 0.021). Furthermore, we noted that gastric tube feeding was associated with a shorter time required to start feeding (WMD: -11.05; p = 0.007)., Conclusions: This research revealed that initiating feeding through the gastric tube required less time compared to postpyloric tube feeding. However, it was also associated with a heightened risk of pneumonia among critically ill patients., Competing Interests: The authors declare no competing interests

Objective: This study aimed to evaluate the effect of continuous control cuff pressure (CCCP) versus intermittent control cuff pressure (ICCP) for the prevention of ventilator-associated pneumonia (VAP) in critically ill patients., Methods: Relevant literature was searched in several databases, including PubMed, Embase, Web of Science, ProQuest, the Cochrane Library, Wanfang Database and China National Knowledge Infrastructure between inception and September 2022. Randomized controlled trials were considered eligible if they compared CCCP with ICCP for the prevention of VAP in critically ill patients. This meta-analysis was performed using the RevMan 5.3 and Trial Sequential Analysis 0.9 software packages. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the level of evidence., Results: We identified 14 randomized control trials with a total of 2080 patients. Meta-analysis revealed that CCCP was associated with a significantly lower incidence of VAP compared with ICCP (relative risk [RR] = 0.52; 95% confidence interval [CI]: 0.37-0.74; P  < 0.001), although considerable heterogeneity was observed ( I 2  = 71%). Conducting trial sequential analysis confirmed the finding, and the GRADE level was moderate. Subgroup analysis demonstrated that CCCP combined with subglottic secretion drainage (SSD) had a more significant effect on reducing VAP (RR = 0.39; 95% CI = 0.29-0.52; P  < 0.001). The effect of CCCP on ventilator-associated respiratory infection (VARI) incidence was uncertain (RR = 0.81; 95% CI = 0.53-1.24; P  = 0.34; I 2  = 61%). Additionally, CCCP significantly reduced the duration of mechanical ventilation (MV) (mean difference [MD] = -2.42 days; 95% CI = -4.71-0.12; P  = 0.04; I 2  = 87%). Descriptive analysis showed that CCCP improved the qualified rate of cuff pressure. However, no significant differences were found in the length of intensive care unit (ICU) stay (MD = 2.42 days; 95% CI = -1.84-6.68; P  = 0.27) and ICU mortality (RR = 0.86; 95% CI = 0.74-1.00; P  = 0.05)., Conclusion: Our findings suggest that the combination of CCCP and SSD can reduce the incidence of VAP and the duration of MV and maintain the stability of cuff pressure. A combination of CCCP and SSD applications is suggested for preventing VAP., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Based on current evidence, there appears to be an association between peri-intubation hypotension and patient morbidity and mortality. Studies have identified shock indices as possible pre-intubation risk factors for peri-intubation hypotension. Thus, we sought to evaluate the association between shock index (SI), modified shock index (MSI), and diastolic shock index (DSI) and peri-intubation hypotension along with other outcomes., Methods: The present study is a sub-study of a randomized controlled trial involving critically ill patients undergoing intubation. We defined peri-intubation hypotension as a decrease in mean arterial pressure <65 mm Hg and/or a reduction of 40% from baseline; or the initiation of, or increase in infusion dosage of, any vasopressor medication (bolus or infusion) during the 30-min period following intubation. SI, MSI, and DSI were analyzed as continuous variables and categorically using pre-established cut-offs. We also explored the effect of age on shock indices., Results: A total of 151 patients were included in the analysis. Mean pre-intubation SI was 1.0  ±  0.3, MSI 1.5  ±  0.5, and DSI 1.9  ±  0.7. Increasing SI, MSI, and DSI were significantly associated with peri-intubation hypotension (OR [95% CI] per 0.1 increase  =  1.16 [1.04, 1.30], P   =  .009 for SI; 1.14 [1.05, 1.24], P   =  .003 for MSI; and 1.11 [1.04, 1.19], P   =  .003 for DSI). The area under the ROC curves did not differ across shock indices (0.66 vs 0.67 vs 0.69 for SI, MSI, and DSI respectively; P   =  .586). Increasing SI, MSI, and DSI were significantly associated with worse sequential organ failure assessment (SOFA) score (spearman rank correlation: r  =  0.30, r  =  0.40, and r  =  0.45 for SI, MSI, and DSI, respectively, all P  < .001) but not with other outcomes. There was no significant impact when incorporating age., Conclusions: Increasing SI, MSI, and DSI were all significantly associated with peri-intubation hypotension and worse SOFA scores but not with other outcomes. Shock indices remain a useful bedside tool to assess the potential likelihood of peri-intubation hypotension., Trial Registration: ClinicalTrials.gov identifier - NCT02105415., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The modified Nutrition Risk in the Critically Ill (mNUTRIC) score was developed to identify patients most likely to benefit from nutritional therapies and to stratify or select subjects for clinical trials. However, the validity of the score and the association between that score and the prognosis of patients in surgical intensive care units (SICUs) remain unclear. This study explored whether the score was a useful prognostic indicator for SICU patients, and whether survival could be improved via nutritional interventions based on mNUTRIC status., Methods: This retrospective observational study enrolled 123 patients admitted to our SICU for critical care from January 2018 to December 2019. Among these, mNUTRIC medical data were available for 116. In-hospital mortality rates were compared based on both mNUTRIC status and the adequacy of nutritional supplementation., Results: mNUTRIC-high status (5 points or more) was apparent in 16 ​% of all critically ill surgical patients. In-hospital mortality was significantly higher in those with mNUTRIC-high scores (42.1 ​% vs. 15.5 ​%, P ​= ​0.023). Both groups exhibited less mortality when nutrition was adequate vs. inadequate (5.0 ​% vs. 40.9 ​% and 26.7 ​% vs. 100 ​%, respectively). In multivariate analysis, mNUTRIC-high scores and inadequate nutritional support were significant risk factors for in-hospital mortality (hazard ratios 7.336 and 13.636, P ​= ​0.027 and 0.002, respectively)., Conclusion: In critically ill surgical patients, those identified as nutritionally high-risk using the mNUTRIC classification had poor in-hospital survival. Moreover, patients who received adequate nutritional support had a better prognosis than those who did not., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group ( P  = .4), stage 2 or 3 AKI (15.9% vs 6%; P  = .98), time to AKI development (1.7 vs 2 days; P  = .5), time to return to baseline renal function (4 vs 3 days; P  = .2), new requirement for RRT (4.5% vs 1.5%; P  = .3), ICU length of stay (7.3 vs 7.4 days; P  = .9), hospital length of stay (19.3 vs 20.1 days; P  = .87), or in-hospital mortality (15.9% vs 10.8%; P  = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P  = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rational: Critically ill surgical patients pose one of the greatest challenges in achieving nutritional goals. Several published papers have demonstrated clear benefits when nutrition support (NS) is managed by a multidisciplinary nutrition support team (NST). We hypothesized that implementing a NST in a surgical intensive care unit (ICU) would increase the number of patients achieving their nutritional goals., Material and Method: Multicenter "BEFORE & AFTER" study. In the BEFORE phase, an audit of the previous state of NS was conducted in three ICUs without a NST., Intervention: Implementation of a NST and protocol. In the AFTER phase, a new audit of NS was conducted. Continuous variables (presented as mean ± SD or median Q1-Q3) were tested using the t-test and Mann-Whitney U test. Categorical variables (presented as frequencies and percentages) were assessed using the chi-square test. A binomial logistic regression model was performed, with independent variables introduced using a stepwise forward method. A difference was considered to be significant with a two-sided P-value <0.05. Statistical analysis was conducted using IBM-SPSS 26., Results: A total of 83 patients were included in the BEFORE phase, and 85 in the AFTER phase. The latter group showed a higher frequency of nutritional risk and malnutrition (SGA B+C odds ratio 2.314, 95% CI 1.164-4.600). Laparoscopy was more frequently utilized as a surgical technique in the AFTER phase. No differences were observed in ICU and hospital LOS or 90 days' survival rates. Two variables remained independent factors to predict NS achievement: NST implementation (odds ratio 3.582, 95% CI 1.733-7.404), and surgical technique (odds ratio 3.231, 95% CI 1.312-7.959)., Conclusion: NST positively impacts the chance of achieving NS goals in critically ill surgical patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andres Martinuzzi reports administrative support, statistical analysis, and writing assistance were provided by NUTRIHOME SA. Andres Martinuzzi reports a relationship with NUTRIHOME SA that includes: employment. Adriana Crivelli reports a relationship with NUTRIHOME SA that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Critically ill adults requiring artificial airways experience profound communication deficits. Studies of interventions supporting communication report disparate outcomes, creating subsequent challenges in the interpretation of their effectiveness. Therefore, we aimed to develop international consensus for a communication core outcome set (Comm-COS) for future trials of communication interventions in this population., Design: 1) Systematic review, 2) patient/family interviews, 3) two-round modified Delphi, and 4) virtual consensus meetings with a final voting round. A multidisciplinary expert steering committee oversaw all stages., Setting: Interviews and consensus meetings were conducted via videoconferencing. Digital methods were used for Delphi and final Comm-COS voting., Subjects: Three stakeholder groups: 1) patient and family members with lived experience within 3 years, 2) clinicians with experience working in critical care, and 3) researchers publishing in the field., Intervention: None., Measurements and Main Results: We identified 59 outcomes via our systematic review, 3 unique outcomes from qualitative interviews, and 2 outcomes from our steering committee. Following item reduction, 32 outcomes were presented in Delphi round 1; 134 participants voted; 15 patient/family (11%), 91 clinicians (68%), and 28 researchers (21%). Nine additional outcomes were generated and added to round 2; 106 (81%) participants voted. Following completion of the consensus processes, the Comm-COS includes seven outcomes: 1) changes in emotions and wellbeing associated with ability to communicate, 2) physical impact of communication aid use, 3) time to functional communication, 4) ability to communicate healthcare needs (comfort/care/safety/decisions), 5) conversation agency, 6) ability to establish a communication connection to develop and maintain relationships, and 7) acceptability of the communication intervention., Conclusions: This is the first COS to specifically focus on communication for critically ill adults. Limitations for operationalization include selection of measures to use with these outcomes. Identification of suitable measures and adoption of the Comm-COS in future trials will help establish effective interventions to ameliorate the highly prevalent and negative experience of communicative incapacity., Competing Interests: Dr. Freeman-Sanderson received support for article research from an internal university seed grant from Faculty of Health, University of Technology Sydney (UTS). Dr. Brodsky’s institution received funding from the National Institutes of Health and the Food and Drug Administration; he received funding from MedBridge and Phagenesis. Dr. Happ received funding from internal research funds, the Healthy State Alliance Momentum grant; she disclosed that she holds the copyright to the Study of Patient-Nurse Effectiveness with Assisted Communication Strategies (SPEACS-2) online communication training program. Sullivan’s institution received funding from UTS. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: To date, age, frailty, and multimorbidity have been used primarily to inform prognosis in older adults. It remains uncertain, however, whether these patient factors may also predict response to critical care interventions or treatment outcomes., Data Sources: We conducted a systematic search of top general medicine and critical care journals for randomized controlled trials (RCTs) examining critical care interventions published between January 1, 2011, and December 31, 2021., Study Selection: We included RCTs of critical care interventions that examined any one of three subgroups-age, frailty, or multimorbidity. We excluded cluster RCTs, studies that did not report interventions in an ICU, and studies that did not report data examining subgroups of age, frailty, or multimorbidity., Data Extraction: We collected study characteristics (single vs. multicountry enrollment, single vs. multicenter enrollment, funding, sample size, intervention, comparator, primary outcome and secondary outcomes, length of follow-up), study population (inclusion and exclusion criteria, average age in intervention and comparator groups), and subgroup data. We used the Instrument for assessing the Credibility of Effect Modification Analyses instrument to evaluate the credibility of subgroup findings., Data Synthesis: Of 2037 unique citations, we included 48 RCTs comprising 50,779 total participants. Seven (14.6%) RCTs found evidence of statistically significant effect modification based on age, whereas none of the multimorbidity or frailty subgroups found evidence of statistically significant subgroup effect. Subgroup credibility ranged from very low to moderate., Conclusions: Most critical care RCTs do not examine for subgroup effects by frailty or multimorbidity. Although age is more commonly considered, the cut-point is variable, and relative effect modification is rare. Although interventional effects are likely similar across age groups, shared decision-making based on individual patient preferences must remain a priority. RCTs focused specifically on critically ill older adults or those living with frailty and/or multimorbidity are crucial to further address this research question., Competing Interests: Dr. Geen received funding from Outro Health. Dr. Ferrante’s institution received funding from the National Institutes of Health (NIH). Dr. Ferrante is supported by a Paul B. Beeson Emerging Leaders in Aging Career Development Award from the National Institute on Aging (K76 AG057203) and the Yale Claude D. Pepper Older Americans Independence Center (P30 AG021342). Drs. Ferrante and Brummel received support for article research from the NIH. Dr. Brummel’s institution received funding from the National Institute on Aging. Dr. Muscedere is the Scientific Director of the Canadian Frailty Network, which is funded by the Government of Canada. Dr. Brummel is supported by the National Institutes of Health under awards R01HD107103 and R01AG077644. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Critically ill patients undergoing extracorporeal membrane oxygenation (ECMO) exhibit unique pharmacokinetics. This study aimed to assess the achievement of vancomycin therapeutic targets in these patients. Methods: This retrospective cohort study included patients on ECMO treated with vancomycin between January 2010 and December 2018. Ninety patients were analyzed based on ECMO connection modality, baseline creatinine levels, estimated glomerular filtration rate (eGFR), renal replacement therapy (RRT) requirements, and vancomycin loading dose administration. Results: Twenty-three percent of the patients achieved the therapeutic range defined by baseline levels. No significant differences in meeting the therapeutic goal were found in multivariate analysis considering ECMO cannulation modality, initial creatinine level, initial eGFR, RRT requirement, or loading dose use. All trough levels between 15 and 20 mcg/mL achieved an estimated area under the curve/minimum inhibitory concentration (AUC/MIC) between 400 and 600, almost all trough levels over 10 mcg/mL predicted an AUC/MIC >400. Discussion: Achieving therapeutic plasma levels in these patients remains challenging, potentially due to factors such as individual pharmacokinetics and pathophysiology. A trough plasma level between 12 and 20 estimated the therapeutic AUC/MIC for all models, proposing a possible lower target, maintaining exposure, and potentially avoiding adverse effects. Despite being one of the largest cohorts of vancomycin use in ECMO patients studied, its retrospective nature and single-center focus limits its broad applicability.

Objectives: Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality., Data Sources: We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024., Study Selection: Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings., Data Extraction: The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928., Data Synthesis: Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87-0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes., Conclusions: Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics., Competing Interests: Dr. Lee’s institution received funding from the Canadian Institutes of Health Research; he received funding from Fonds de Recherche Quebec—Sante. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The decision to forgo life-sustaining treatment in intensive care units (ICUs) is influenced by ethical, cultural, and medical factors. This study focuses on a population of patients with hospital-acquired bloodstream infections (HABSI) to investigate the association between patient, pathogen, center and country-level factors and these decisions., Methods: We analyzed data from the EUROBACT-2 study (June 2019-January 2021) from 265 centers worldwide, focusing on non-COVID-19 patients who died in the hospital or within 28 days after HABSI. We assessed whether death was preceded by a decision to forgo life-sustaining treatment, examining country, center, patient, and pathogen variables. To assess the association of each potentially important variable with the decision to forgo life-sustaining treatment, univariable mixed logistic regression models with a random center effect were performed., Results: Among 1589 non-COVID-19 patients, 519 (32.7%) died, with 191 (36.8%) following a decision to forgo life-sustaining treatment. Significant geographical differences were observed, with no reported decisions to forgo life-sustaining treatment in African countries and fewer in the Middle East compared to Western Europe, Australia, and Asia. Once a center effect was considered, only health expenditure (Odds ratio 1.79, 95%CI: 1.45-2.21, p < 0.01) and age (Odds ratio 1.02, 95%CI: 1.002-1.05, p = 0.03) were significantly associated with decisions to forgo life-sustaining treatment, while other patient and pathogen factors were not., Conclusion: Economic and regional disparities significantly impact end-of-life decision-making in ICUs. Global policies should consider these disparities to ensure equitable end-of-life care practices., (© 2024. The Author(s).)

Introduction: Objective: this study aimed to assess the effects of two isocaloric parenteral nutrition (PN) regimens with different protein content and non-protein calorie to nitrogen ratio (NPCNR) on the evolution of nutritional parameters and outcomes in adult inpatients. Methods: this was a retrospective quasi-experimental study performed in a 400-bed tertiary hospital. Adult inpatients were initially eligible if they had received ≥ 4 days of PN with NPCNR ≥ 100 or ≤ 90 in a period of three years. Patients were propensity-score matched to adjust for differences, resulting in two final cohorts: Cohort "Medium-P" included patients receiving PN with NCPCNR ≥ 100 and cohort "High-P", receiving PN with NCPCNR ≤ 90. The main variables were differences in plasma albumin, prealbumin, cholesterol, and lymphocyte count, days requiring PN, length of stay, and mortality at 90 days. Results: 202 patients were finally recruited and divided into the two equal cohorts. Patients were mainly male (122; 60.4 %), surgical (149; 73.8 %), critically ill (100; 49.5 %), with high nutritional risk (141; 69.8 %) and with a neoplasm (145; 71.8 %). PN provided 25 kcal/kg/day, but protein intake was 0.25 g/kg/day higher in the "High-P" cohort. Baseline characteristics and biochemistry were not different between the two cohorts. The "High-P" cohort presented a smaller difference at the end of PN for lymphocytes, more days with hyperglycaemia, and more days requiring PN. The rest of variables did not differ. Conclusions: high doses of protein (lower NPCNR) did not present advantages compared to medium doses of protein (higher NPCNR) when providing isocaloric PN in adult inpatients.

Introduction: Introduction: medical nutritional treatment (MNT) can be complex and may be associated with potential metabolic complications, which has been recently described as nutritrauma. Objective: the aim of our work is to describe whether the application of the nutritrauma concept in real life is feasible and useful to detect the metabolic complications associated with the prescription of MNT. Material and methods: in this descriptive, prospective study at a single center we enrolled 30 consecutive critically ill patients in a 14-bed medical-surgical intensive care unit. The nutritrauma strategy implementation was based in four "M" steps: Metabolic screening, MNT prescription, biochemical Monitoring, and nutritional Management. Results: we analyzed 28 patients (mean age, 69.7 ± 11.3 years; APACHE II, 18.1 ± 8.1; SOFA, 7.5 ± 3.7; Nutric Score, modified, 4.3 ± 2.01, and mean BMI, 27.2 ± 3.8). The main cause of admission was sepsis (46.4 %). Length of ICU stay was 20.6 ± 15.1 days; 39.3 % of subjects died during their ICU stay. Enteral nutrition (82.1 %) was more frequent than parenteral nutrition (17.9 %). During nutritional monitoring, 54 specific laboratory determinations were made. Hyperglycemia was the most frequent metabolic alteration (83.3 % of measurements). Electrolyte disturbances included hypocalcemia (50 %), hypophosphatemia (29.6 %) and hypokalemia (27.8 %). The most frequent lipid profile abnormalities were hypocholesterolemia (64.8 %) and hypertriglyceridemia (27.8 %). Furthermore, nutritional prescription was modified for 53.6 % of patients: increased protein dosage (25 %), increased calorie dosage (21.4 %) and change to organ-specific diet (17.8 %). Conclusions: in conclusion, the application of the nutritrauma approach facilitates detection of metabolic complications and an evaluation of the appropriate prescription of MNT.

Background: The objective of this study was to evaluate the association between noninvasive ventilation (NIV) compared with invasive ventilation and mortality in subjects with severe acute respiratory infection., Methods: This was a retrospective multi-center study of subjects with severe acute respiratory infection treated with ventilatory support between September 2012 and June 2018. We compared the 90-d mortality of subjects managed initially with NIV (NIV group) with those managed with invasive ventilation only (invasive ventilation group), adjusting by propensity score., Results: Of 383 subjects, 189 (49%) were in the NIV group and 194 (51%) were in the invasive ventilation group. Of the subjects initially treated with NIV, 117 (62%) were eventually intubated. Crude 90-d mortality was lower in the NIV group versus the invasive ventilation group (42 [22.2%] vs 77 [39.7%]; P < .001). After propensity score adjustment, NIV was associated with lower 90-d mortality than invasive ventilation (odds ratio 0.54, 95% CI 0.38-0.76; P < .001). The association of NIV with mortality compared with invasive ventilation was not different across the studied subgroups., Conclusions: In subjects with severe acute respiratory infection and acute respiratory failure, NIV was commonly used. NIV was associated with a lower 90-d mortality. The observed high failure rate suggests the need for further research to optimize patient selection and facilitate early recognition of NIV failure., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: A protocolized extubation readiness test (ERT), including a spontaneous breathing trial (SBT), is recommended for patients who are intubated. This quality-improvement project aimed to improve peri-extubation outcomes by using a high-risk ERT protocol in intubated cardiac patients in addition to a standard-risk protocol., Methods: After baseline data collection, we implemented a standard-risk ERT protocol (pressure support plus PEEP), followed by a high-risk ERT protocol (PEEP alone) in cardiac subjects who were intubated. The primary outcome, a composite of extubation failure and rescue noninvasive respiratory support, was compared between phases. Ventilator duration and use of postextubation respiratory support were balancing measures., Results: A total of 213 cardiac subjects who were intubated were studied, with extubation failure and rescue noninvasive respiratory support occurring in 10 of 213 (4.7%) and 8 of 213 (3.8%), respectively. We observed a reduction in the composite outcome among the 3 consecutive phases (5/29 [17.2%], 10/110 [9.1%] vs 3/74 [4.1%]; P = .10), but this did not reach statistical significance. In the logistic regression model when adjusting for admission type, the high-risk ERT protocol was associated with a significant reduction of the composite outcome (adjusted odds ratio 0.20, 95% CI 0.04-0.091; P = .037), whereas the standard-risk ERT protocol was not (adjusted odds ratio 0.48, 95% CI 0.15-1.53; P = .21). This was not accompanied by a longer ventilator duration (2.0 [1.0, 3.0], 2.0 [1.0-4.0], vs adjusted odds ratio 2.0 [95% [1.0-6.0]; P = .99) or an increased use of planned noninvasive respiratory support (10/29 [35.5%], 35/110 [31.8%], vs 25/74 [33.8%]; P > .99)., Conclusions: In this quality-improvement project, a high-risk ERT protocol was implemented with improvement in peri-extubation outcomes among cardiac subjects., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Objective: The objective of this study was to explore factors that affect the clearance of imipenem in critically ill patients and to provide a dosing regimen for such patients., Methods: A prospective open-label study enrolled 51 critically ill patients with sepsis. Patients were between the ages of 18 and 96. Blood samples were collected in duplicate before (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after imipenem administration. The plasma imipenem concentration was determined by the high-performance liquid chromatography-ultraviolet detection (HPLC-UV) method. A population pharmacokinetic (PPK) model was developed using nonlinear mixed-effects modelling methods to identify covariates. Monte Carlo simulations were performed using the final PPK model to explore the effect of different dosing regimens on the probability of target attainment (PTA)., Results: The imipenem concentration data were best described by a two-compartment model. Creatinine clearance (CrCl, mL/min) was a covariate that affected central clearance (CLc). Patients were divided into four subgroups based on different CrCl rates. Monte Carlo simulations were performed to assess the PTA differences between empirical dosing regimens (0.5 g every 6 hours (q6h), 0.5 g every 8 hours (q8h), 0.5 g every 12 hours (q12h), 1 g every 6 hours (q6h), 1 g every 8 hours (q8h), and 1 g every 12 hours (q12h)) and to determine the target achievement rate covariate., Conclusion: This study identified covariates for CLc, and the proposed final model can be used to guide clinicians administering imipenem in this particular patient population., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: This study aims to evaluate a novel prone position ventilation device designed to enhance patient safety, improve comfort, and reduce adverse events, facilitating prolonged tolerance in critically ill patients., Methods: A randomized controlled trial was conducted on 60 critically ill patients from January 2020 to June 2023. Of which, one self-discharged during treatment and another was terminated due to decreased oxygenation, leaving an effective sample of 58 patients. Patients were allocated to either a control group receiving traditional prone positioning aids (ordinary sponge pads and pillows) or an intervention group using a newly developed adjustable prone positioning device. A subset of patients in each group also received life support technologies such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). We assessed prone position ventilation tolerance, oxygen saturation increments postintervention, duration of prone positioning, CRRT filter lifespan, and the incidence of adverse events., Results: The intervention group exhibited significantly longer average tolerance to prone positioning (16.6 hours vs. 8.3 hours, P < 0.001 with a difference of 8.3 (4.4, 12.2) hours), higher increases in oxygen saturation postventilation (9% vs. 6%, P < 0.001 with a difference of 3.0 (1.5, 4.5)), and reduced time required for medical staff to position patients (11.7 min vs. 21.8 min, P < 0.001 with a difference of -10.1 (-11.9, -8.3)). Adverse events, including catheter displacement or blockage, facial edema, pressure injuries, and vomiting or aspiration, were markedly lower in the intervention group, with statistical significance ( P < 0.05). In patients receiving combined life support, the intervention group demonstrated improved catheter blood drainage and extended CRRT filter longevity., Conclusion: The newly developed adjustable prone ventilation device significantly improves tolerance to prone positioning, enhances oxygenation, and minimizes adverse events in critically ill patients, thereby also facilitating the effective application of life support technologies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Yufeng Li et al.)

Purpose: The purpose of this therapeutic update is to provide pharmacists with a general overview of the pathophysiology of hyperchloremia and describe strategies to help prevent development of this electrolyte abnormality in hospitalized patients., Summary: Hyperchloremia is an electrolyte abnormality associated with an increased incidence of acute kidney injury and metabolic acidosis. Intravenous (IV) fluids utilized for volume resuscitation, medication diluents, and total parental nutrition all may contribute to the development of hyperchloremia. Current evidence suggests that administration of balanced crystalloids for either fluid resuscitation or maintenance fluids may impact serum chloride levels and patient outcomes. In multiple randomized controlled trials, administering balanced crystalloids for fluid resuscitation in critically ill patient populations did not decrease mortality. However, further analyses of subpopulations within these trials have demonstrated that patients with sepsis may benefit from receiving balanced crystalloids for initial fluid resuscitation. Results from several small studies suggest that altering the composition of these IV fluids may help prevent development of hyperchloremia., Conclusion: Management of hyperchloremia is preventative in nature and can be mitigated through management of resuscitation fluids, medication diluents, and total parenteral nutrition. Inpatient pharmacists should be aware of the potential risk of fluid-associated hyperchloremia and assist with optimal fluid management to prevent and manage hyperchloremia., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day)., Methods: The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m 2 , kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants., Findings: Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups., Interpretation: High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission., Funding: Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre., Competing Interests: Declaration of interests EDW receives honoraria for scientific lectures from Baxter Healthcare, Nutricia–Danone, and Nestlé. ARHvZ receives grants from AOP Pharma, Nutricia–Danone, Fresenius Kabi, PAION, and Rousselot; receives consulting fees from AOP Pharma, Medcaptain, and PAION; receives honoraria for lectures from Abbott, AOP Pharma, Baxter, Nestlé, Nutricia–Danone, Fresenius Kabi, GE Healthcare, and Dutch Medical Food; receives support for travel from Nutricia–Danone and Dutch Medical Food; is a member of the adult intensive care unit patient nutrition guideline committee of the European Society for Clinical Nutrition and Metabolism, the executive team of SepsisNet Netherlands, and the executive team of the Netherlands Society for Parenteral and Enteral Nutrition; and is the European Society of Intensive Care Medicine Section Feeding, Rehabilitation Endocrinology and Metabolism chair. ZP receives grants from Fresenius Kabi, Nestlé, and Baxter; receives consulting fees from Fresenius Kabi, Nestlé, Baxter, Faraday Pharmaceuticals, and Bioage Pharmaceuticals; and receives honoraria for lectures from Baxter, Nestlé, Fresenius Kabi, and Nutricia. MCGvdP receives grants from the Netherlands Organisation of Health Research and Development and the Belgian Health Care Knowledge Centre; receives in-kind support from Nutricia; receives consulting fees from Nutricia and Nestlé; and receives honoraria for lectures and support for travel from Nutricia. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Invasive devices are routinely used in the care of critically ill patients. Although they are often essential components of patient care, devices such as intravascular catheters, endotracheal tubes, and ventilators are a common source of complications in the intensive care unit. Critical care practitioners who use these devices need to use strategies for risk reduction and understand approaches to management when adverse events occur. This review discusses the identification, prevention, and management of complications of vascular, airway, and mechanical support devices commonly used in the intensive care unit., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

In critical illness the regulation of inflammation and oxidative stress can improve patient outcomes, and thus omega-3 polyunsaturated fatty acids (PUFAs) have been used as part of parenteral nutrition (PN) owing to their potential anti-inflammatory effects. The international lipids in PN Summit, encompassed discussions and the production of consensus guidelines concerning PN intravenous lipid emulsion (ILE) use in critical care. The Lipid Summit participants agreed that the inclusion of fish oil in ILEs is associated with meaningful clinical benefits without signals of harm, based on a strong biological rationale and current clinical evidence. Decisions concerning ILE choice should be made based on current evidence, thus addressing clinical requirements for guidance, particularly as further definitive evidence seems unlikely to occur. In addition, a future of individualized ICU care is envisioned, yielding better clinical outcomes. This approach will require the greater use of intelligent study designs incorporating the use of biomarkers of omega-3 derivatives, inflammatory-resolving processes, and/or muscle protein breakdown., (© 2024. The Author(s).)

Most randomized controlled studies on nutrition in intensive care patients did not yield conclusive results or were neutral or negative concerning the primary endpoints but also in most secondary endpoints. However, there is a consistent observation that in several of these studies there was a negative effect of the nutrition intervention on the kidneys in one of the study arms. During the early phase and in unstable periods during further course of disease an inadequate clinical nutrition can damage the kidneys, can elicit or aggravate acute kidney injury and/ or increase requirements of renal replacement therapy (RRT). This relates to total energy intake, glucose intake/hyperglycemia and protein/ amino acid intake at various stages of renal dysfunction. The kidney could present a critical organ system for guiding nutrition therapy, a close monitoring of kidney function should be observed and nutrition therapy may need to be adapted accordingly. The long-held dogma of performing full nutrition and accept an otherwise not necessary RRT is definitely to be refuted., (© 2024. The Author(s).)

Background: Advances in emergency and critical care have improved outcomes, but gaps in communication and decision-making persist, especially in the emergency department (ED), prompting the development of a checklist to aid in serious illness conversations (SIC) in China., Methods: This was a single-centre prospective interventional study on the quality improvement of SIC for life-sustaining treatment (LST). The study recruited patients consecutively for both its observational baseline and interventional stages until its conclusion. Eligible participants were adults over 18 years old admitted to the Emergency Intensive Care Unit (EICU) of a tertiary teaching hospital, possessing full decisional capacity or having a legal proxy. Exclusions were made for pregnant women, patients deceased upon arrival, those who refused participation, and individuals with incomplete data for analysis. First, a two-round Delphi process was organized to identify major elements and generate a standard process through a checklist. Subsequently, the efficacy of SIC in adult patients admitted to the EICU was compared using the Decisional Conflict Scale (DCS) score before (baseline group) and after (intervention group) implementing the checklist., Results: The study participants presented with the most common comorbidities, such as diabetes, myocardial infarction, cerebrovascular disease, moderate-to-severe renal disease, congestive heart failure, and chronic pulmonary disease. The median Charlson Index did not differ between the baseline and intervention cohorts. The median length of hospital stay was 11.0 days, and 82.9% of patients survived until hospital discharge. The total DCS score was lower in the intervention group than in the baseline group. Three subscales, including the informed, values clarity, and support subscales, demonstrated significant differences between the intervention and baseline groups. Fewer intervention group patients agreed with and changed their minds about cardiopulmonary resuscitation (CPR) compared to the baseline group., Conclusion: The use of a SIC checklist in the EICU reduced the DCS score by increasing medical information disclosure, patient value awareness, and decision-making support., (© 2024. The Author(s).)

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates., Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo., Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation., Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days., Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL., Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen., Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown., Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction., Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023., Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first., Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models., Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group., Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin., Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Early diagnosis and prompt management are essential to enhance the outcomes of patients with sepsis and septic shock. Over the past two decades, evidence-based guidelines have guided appropriate treatment and recommended the implementation of a bundle strategy to deliver fundamental treatments within the initial hours of care. Shortly after its introduction, the implementation of a bundle strategy has led to a substantial decrease in mortality rates across various health care settings. The primary advantage of these bundles is their universality, making them applicable to all patients with sepsis. However, this same quality also represents their primary disadvantage as it fails to account for the significant heterogeneity within the septic patient population. Recently, the individualization of treatments included in the bundle has been suggested as a potential strategy for further improving the prognosis of patients with sepsis. New strategies for the early identification of microorganisms and their resistance patterns, advanced knowledge of antibiotic kinetics in critically ill patients, more conservative fluid therapy in specific patient populations, and early use of alternative vasopressors to catecholamines, as well as tailored source control based on patient conditions and site of infection, are potential approaches to personalize initial care for specific subgroups of patients. These innovative methodologies have the potential to improve the management of septic shock. However, their implementation in clinical practice should be guided by solid evidence. Therefore, it is imperative that future research evaluate the safety, efficacy, and cost-effectiveness of these strategies., Competing Interests: M.G. has received honoraria for speaking at conferences and advisory services from Biomerieux, Thermofischer, Pfizer, MSD, Gilead, Shionogi, AOP Pharma, and Viatris related to the topic of this study. The other authors declare that they have no conflict of interest related to the topic of this study., (Thieme. All rights reserved.)

The management of sedation in intensive care medicine has changed substantially in the last few years. Neuromuscular blocking agents (NMBA) are only rarely indicated in modern intensive care medicine. In this review, the mechanism of action, potential side effects, and special considerations for the application of NMBA to critically ill patients will be discussed. We further present the rationale for the use of NMBA for the remaining indications, such as endotracheal intubation, selected cases of severe acute respiratory distress syndrome, and shivering during temperature control after cardiac arrest. The review will close with a description of potential side effects of NMBA use in the intensive care setting, such as awareness, acquired skeletal muscle weakness as well as corneal injuries, and how monitoring of sedation and peripheral muscle blockade may be handled., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen CJ ist Mitglied in der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI)., (Thieme. All rights reserved.)

The current S3 guideline, "Positioning Therapy and Mobilization of Critically Ill Patients in Intensive Care Units", introduces methodological changes and substantive updates compared to the previous version. Additionally, new evidence-based insights with specified PICO questions have been integrated, aiming for a more precise application of recommendations in clinical practice and thus enhancing the care of critically ill patients.A notable aspect is the more nuanced approach to early mobilization, which is recommended to commence within the first 72 hours of ICU admission. A staged concept and score-based mobilization schema facilitate improved patient rehabilitation. Mobilization should be standard of care, i.e., immobilization should be ordered by the physician. The guideline provides suggestions for the duration and additional mobilization measures to ensure patients stand, transfer actively from bed to chair, or walk as frequently as possible. These recommendations apply even during ECMO therapy, highlighting the importance of early mobilization.Further updates include semi-recumbent positions of at least 40° in intubated patients, with careful consideration of potential side effects. Continuous lateral rotation therapy (CLRT) is not advised due to the progress in intensive care therapy, shifting from deep sedation toward responsive patient management.Prone positioning (PP) involves rotating the patient 180° onto the ventral side. It is recommended as a therapeutic option for invasively ventilated patients with ARDS and impaired arterial oxygenation (PaO 2 /FiO 2 <150mmHg), with a recommended minimum duration of 12 hours, ideally 16 hours. Special recommendations apply, for example, to COVID-19 patients with acute hypoxemic respiratory failure, where awake proning should be considered.Additionally, new chapters have been introduced focusing on assistive devices and neuromuscular electrical stimulation., Competing Interests: C. Hermes: VG Wort Lizenzgebühren. Bezahlung oder Honorare für Vorträge, Präsentationen, oder Bildungsveranstaltungen: Atmos, Getinge, Arjo, TapMed. Reisekostenerstattung für wissenschaftliche Vorträge durch DIVI; DGIIN; DBfK; GFO. Mitglied: DGIIN (Vorstand), DGF, DBfK, DIVI, DGP, Pflegekammer NRW (Vorstand). Peter Nydahl gibt an das es keinen COI im Zusammenhang mit dem Manuskript gibt. Julius J. Grunow gibt an das es keinen COI im Zusammenhang mit dem Manuskript gibt. Stefan J Schaller gibt an: erhielt Fördermittel und nicht-finanzielle Unterstützung von Reactive Robotics GmbH (München, Deutschland), ASP GmbH (Attendorn, Deutschland), STIMIT AG (Biel, Schweiz), ESICM (Genf, Schweiz), Fördermittel, persönliche Honorare und nicht-finanzielle Unterstützung von Fresenius Kabi Deutschland GmbH (Bad Homburg, Deutschland), Fördermittel aus dem Innovationsfond des Gemeinsamen Bundesausschusses (G-BA), persönliche Honorare der Springer Verlag GmbH (Wien, Österreich) für Fortbildungszwecke und der Advanz Pharma GmbH (Bielefeld, Deutschland), nicht-finanzielle Unterstützung von nationalen und internationalen Gesellschaften (und deren Kongressveranstaltern) auf dem Gebiet der Anästhesiologie und Intensivmedizin, außerhalb der eingereichten Arbeit. Dr. Schaller hält in geringem Umfang Aktien von Alphabet Inc., der Bayer AG und der Siemens AG; diese Beteiligungen haben keine Entscheidungen bezüglich seiner Forschung oder dieser Arbeit beeinflusst., (Thieme. All rights reserved.)

Importance: The effectiveness of daily sedation interruption (DSI, defined as temporary interruption of sedation) has yet to be demonstrated in critically ill pediatric patients., Objective: To compare the clinical outcomes of DSI vs continuous intravenous (IV) sedation in patients receiving invasive mechanical ventilation (MV) support in the pediatric intensive care unit (PICU)., Data Sources: A systematic search for studies was conducted using predefined keywords and Medical Subject Headings in 5 major databases (PubMed, Embase, Web of Science, CINAHL [Cumulated Index to Nursing and Allied Health Literature], and Cochrane Central Register of Controlled Trials) from database inception to October 31, 2023., Study Selection: Retrospective and prospective observational studies, randomized clinical trials (RCTs), and systematic reviews were assessed for inclusion. Studies were eligible if they compared DSI to continuous IV sedation in patients aged 18 years or younger requiring MV in the PICU., Data Extraction and Synthesis: Study characteristics, including the types of sedation, sedation protocols, and clinical outcomes, were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. A random-effects model was used to pool results from articles for the meta-analysis., Main Outcomes and Measures: The primary outcomes of interest were duration of MV and length of PICU stay. Secondary outcomes included total sedative dose requirement, adverse events (eg, complications associated with MV, withdrawal, and delirium), and mortality., Results: A total of 6 RCTs with 2810 pediatric patients (1569 males [55.8%]; mean age, 26.5 [95% CI, 15.0-37.9] months) were included in the final analysis; patients had a mean PRISM (Pediatric Risk of Mortality) score of 13.68 (95% CI, 10.75-16.61). Compared with continuous IV sedation, DSI was associated with a reduction in length of PICU stay (5 studies, n = 2770; mean difference [MD], -1.45 [95% CI, -2.75 to -0.15] days; P = .03]. There was no difference in MV duration (5 studies, n = 2750; MD, -0.93 [95% CI, -1.89 to 0.04] days; P = .06), total doses of midazolam (3 studies, n = 191; MD, -1.66 [95% CI, -3.95 to 0.63] mg/kg) and morphine used (2 studies, n = 189; MD, -2.63 [95% CI, -7.01 to 1.75] mg/kg), or adverse events (risk ratio [RR], 1.03 [95% CI, 0.74-1.42]; P = .88). There was no difference in mortality between patients exposed vs not exposed to DSI (RR, 0.89 [95% CI, 0.55-1.46]; P = .65)., Conclusions and Relevance: This systematic review and meta-analysis found that use of DSI in pediatric patients was associated with reduced length of PICU stay with no increase in adverse events. Further research is needed to ascertain whether this strategy is associated with improved neurodevelopmental outcomes in PICU survivors.

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

A scientific panel was created consisting of 23 interdisciplinary and interprofessional experts in intensive care medicine, physiotherapy, nursing care, surgery, rehabilitative medicine, and pneumology delegated from scientific societies together with a patient representative and a delegate from the Association of the Scientific Medical Societies who advised methodological implementation. The guideline was created according to the German Association of the Scientific Medical Societies (AWMF), based on The Appraisal of Guidelines for Research and Evaluation (AGREE) II. The topics of (early) mobilisation, neuromuscular electrical stimulation, assist devices for mobilisation, and positioning, including prone positioning, were identified as areas to be addressed and assigned to specialist expert groups, taking conflicts of interest into account. The panel formulated PICO questions (addressing the population, intervention, comparison or control group as well as the resulting outcomes), conducted a systematic literature review with abstract screening and full-text analysis and created summary tables. This was followed by grading the evidence according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence and a risk of bias assessment. The recommendations were finalized according to GRADE and voted using an online Delphi process followed by a final hybrid consensus conference. The German long version of the guideline was approved by the professional associations. For this English version an update of the systematic review was conducted until April 2024 and recommendation adapted based on new evidence in systematic reviews and randomized controlled trials. In total, 46 recommendations were developed and research gaps addressed., (© 2024. The Author(s).)

Background: Extracorporeal membrane oxygenation (ECMO) is used in critically ill children with cardiac and/or respiratory failure. Use is increasing in children with high-risk comorbidities. Reasons children do not survive ECMO are poorly described., Aims: Describe characteristics and cause of death, compare mortality in children with high-risk comorbidities, evaluate mortality trends over a decade., Method: All children <18 years old who received ECMO at this institution from 1 January 2011 to 31 December 2020 were described and categorised by outcome: died on or <48 h post-ECMO, died ≥48 h post-ECMO, survived to hospital discharge. Children who did not survive ECMO (DNSE) were categorised to: ECMO withdrawal for irrecoverable original condition, withdrawal for poor prognosis neurological condition, brain death, withdrawal for poor prognosis with multiple complex conditions, and unsupportable. Poison regression was used to analyse survival trends., Results: Four hundred twenty-eight children received ECMO, 19% DNSE, 14% died ≥48 h post-ECMO and 67% survived. ECMO was electively withdrawn for irrecoverable original condition (39%), poor prognosis for neurological condition (32%) or multiple complex conditions (18%). One hundred twenty-two children had ≥1 high-risk comorbidity. Children with genetic syndromes (58%), risk-adjusted congenital heart surgery score-1 ≥4 (53%), primary immunodeficiency (50%) had lower hospital survival. No children with malignancy/bone marrow transplant survived to hospital discharge. Overall hospital survival was 67%, with no significant change during the study period (P-trend = 0.99)., Conclusion: Children who DNSE have therapy electively withdrawn for irrecoverable disease or poor prognosis. Children with high-risk comorbidities have a reasonable chance of survival. This study informs clinicians ECMO may be a therapeutic option., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Delirium is a heterogeneous syndrome characterized by an acute change in level of consciousness that is associated with inattention and disorganized thinking. Delirium affects most critically ill patients and is associated with poor patient-oriented outcomes such as increased mortality, longer ICU and hospital length of stay, and worse long-term cognitive outcomes. The concept of delirium and its subtypes has existed since nearly the beginning of recorded medical literature, yet robust therapies have yet to be identified. Analogous to other critical illness syndromes, we suspect the lack of identified therapies stems from patient heterogeneity and prior subtyping efforts that do not capture the underlying etiology of delirium. The time has come to leverage machine learning approaches, such as supervised and unsupervised clustering, to identify clinical and pathophysiological distinct clusters of delirium that will likely respond differently to various interventions. We use sedation in the ICU as an example of how precision therapies can be applied to critically ill patients, highlighting the fact that while for some patients a sedative drug may cause delirium, in another cohort sedation is the specific treatment. Finally, we conclude with a proposition to move away from the term delirium, and rather focus on the treatable traits that may allow precision therapies to be tested., Competing Interests: Dr. Prendergast received funding from McGraw-Hill; he received support for article research from the National Institutes of Health; he disclosed off-label use of antipsychotic agents to treat delirium. Dr. Boyd’s institution received funding from the Canadian Institute of Health Research; he received funding from Ontario Health-Trillium Gift of Life Network. Dr. Potter has disclosed that she does not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)