Hypophosphatemia after Start of Medical Nutrition Therapy Indicates Early Refeeding Syndrome and Increased Electrolyte Requirements in Critically Ill Patients but Has No Impact on Short-Term Survival.

Refeeding syndrome (RFS) is a potentially life-threatening complication in malnourished (critically ill) patients. The presence of various accepted RFS definitions and the inclusion of heterogeneous patient populations in the literature has led to discrepancies in reported incidence rates in patients requiring treatment at an intensive care unit (ICU). We conducted a prospective observational study from 2010 to 2013 to assess the RFS incidence and clinical characteristics among medical ICU patients at a large tertiary center. RFS was defined as a decrease of more than 0.16 mmol/L serum phosphate to values below 0.65 mmol/L within seven days after the start of medical nutrition therapy or pre-existing serum phosphate levels below 0.65 mmol/L. Overall, 195 medical patients admitted to the ICU were included. RFS was recorded in 92 patients (47.18%). The presence of RFS indicated significantly altered phosphate and potassium levels and was accompanied by significantly more electrolyte substitutions (phosphate, potassium, and magnesium). No differences in fluid balance, energy delivery, and insulin requirements were detected. The presence of RFS had no impact on ICU length of stay and ICU mortality. Screening for RFS using simple diagnostic criteria based on serum phosphate levels identified critically ill patients with an increased demand for electrolyte substitutions. Therefore, stringent monitoring of electrolyte levels is indicated to prevent life-threatening complications.

Does red blood cell transfusion affect clinical outcomes in critically ill patients? A report from a large teaching hospital in south Iran.

BACKGROUND: Despite the beneficial effects, RBC transfusion can be associated with infectious and non-infectious complications in critically ill patients. OBJECTIVES: Investigate current RBC transfusion practices and their effect on the clinical outcomes of patients in intensive care units (ICUs). DESIGN: Retrospective observational study. SETTING: Three mixed medical-surgical adult ICUs of a large academic tertiary hospital. PATIENTS AND METHODS: From March 2018 to February 2020, all adult patients admitted to medical or surgical ICU. Patients who received one or more RBC transfusions during the first month of ICU admission were included in the "transfusion" group, while the remaining patients were assigned to the "non-transfusion" group. MAIN OUTCOME MEASURES: Mortality and length of ICU and hospital stay. SAMPLE SIZE: 2159 patients. RESULTS: Of 594 patients who recieved transfusions, 27% of patients received red blood cell (RBC) products. The mean pre-transfusion hemoglobin (Hb) level was 8.05 (1.46) g/dL. There was a significant relationship between higher APACHE II scores and ICU mortality in patients with Hb levels of 7-9 g/dL (OR adjusted=1.05). Also, ICU mortality was associated with age (OR adjusted=1.03), APACHE II score (OR adjusted=1.08), and RBC transfusion (OR adjusted=2.01) in those whose Hb levels were >9 (g/dl). CONCLUSION: RBC transfusion was associated with an approximately doubled risk of ICU mortality in patients with Hb>9 g/dL. High APACHE II score and age increase the chance of death in the ICU by 8% and 3%, respectively. Hence, ICU physicians should consider a lower Hb threshold for RBC transfusion, and efforts must be made to optimize RBC transfusion practices. LIMITATIONS: Single-center and retrospective study.

Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies.

An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.

Anti-inflammatory therapies are associated with delayed onset of anemia and reduction in transfusion requirements in critically ill patients: results from two studies.

BACKGROUND: Anemia is a hallmark of critical illness, which is largely inflammatory driven. We hypothesized that the use of anti-inflammatory agents limits the development of anemia and reduces the need for red blood cell (RBC) transfusions in patients with a hyper-inflammatory condition due to COVID-19. METHODS: An observational cohort (n = 772) and a validation cohort (a subset of REMAP-CAP, n = 119) of critically ill patients with hypoxemic respiratory failure due to COVID-19 were analyzed, who either received no treatment, received steroids or received steroids plus IL-6 blocking agents. The trajectory of hemoglobin (Hb) decline and the need for RBC transfusions were compared using descriptive statistics as well as multivariate modeling. RESULTS: In both cohorts, Hb level was higher in the treated groups compared to the untreated group at all time points. In the observational cohort, incidence and number of transfused patients were lower in the group receiving the combination treatment compared to the untreated groups. In a multivariate analysis controlling for baseline Hb imbalance and mechanical ventilation, receipt of steroids remained associated with a slower decline in Hb level and the combination treatment remained associated with a slower decline of Hb and with less transfusions. Results remained the same in the validation cohort. CONCLUSION: Immunomodulatory treatment was associated with a slower decline in Hb level in critically ill patients with COVID-19 and with less transfusion. Findings point toward inflammation as an important cause for the occurrence of anemia in the critically ill.

Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

Continuation of chronic antiplatelet therapy is not associated with increased need for transfusions: a cohort study in critically ill septic patients.

BACKGROUND: The decision to maintain or halt antiplatelet medication in septic patients admitted to intensive care units presents a clinical dilemma. This is due to the necessity to balance the benefits of preventing thromboembolic incidents and leveraging anti-inflammatory properties against the increased risk of bleeding. METHODS: This study involves a secondary analysis of data from a prospective cohort study focusing on patients diagnosed with severe sepsis or septic shock. We evaluated the outcomes of 203 patients, examining mortality rates and the requirement for transfusion. The cohort was divided into two groups: those whose antiplatelet therapy was sustained (n = 114) and those in whom it was discontinued (n = 89). To account for potential biases such as indication for antiplatelet therapy, propensity score matching was employed. RESULTS: Therapy continuation did not significantly alter transfusion requirements (discontinued vs. continued in matched samples: red blood cell concentrates 51.7% vs. 68.3%, p = 0.09; platelet concentrates 21.7% vs. 18.3%, p = 0.82; fresh frozen plasma concentrates 38.3% vs. 33.3%, p = 0.7). 90-day survival was higher within the continued group (30.0% vs. 70.0%; p < 0.001) and the Log-rank test (7-day survivors; p = 0.001) as well as Cox regression (both matched samples) suggested an association between continuation of antiplatelet therapy < 7 days and survival (HR: 0.24, 95%-CI 0.10 to 0.63, p = 0.004). Sepsis severity expressed by the SOFA score did not differ significantly in matched and unmatched patients (both p > 0.05). CONCLUSIONS: The findings suggest that continuing antiplatelet therapy in septic patients admitted to intensive care units could be associated with a significant survival benefit without substantially increasing the need for transfusion. These results highlight the importance of a nuanced approach to managing antiplatelet medication in the context of severe sepsis and septic shock.

Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis.

BACKGROUND: To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets. METHODS: Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT>4xMIC, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method. RESULTS: A total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15-2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01-0.29). Male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2. CONCLUSIONS: Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.

Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial.

INTRODUCTION: An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes. METHODS AND ANALYSIS: This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored. ETHICS AND DISSEMINATION: All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement. TRIAL REGISTRATION NUMBER: NCT03653832.

The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients.

While several effective therapies for critically ill patients with COVID-19 have been identified in large, well-conducted trials, the mechanisms underlying these therapies have not been investigated in depth. Our aim is to investigate the association between various immunosuppressive therapies (corticosteroids, tocilizumab and anakinra) and the change in endothelial host response over time in critically ill COVID-19 patients. We conducted a pre-specified multicenter post-hoc analysis in a Dutch cohort of COVID-19 patients admitted to the ICU between March 2020 and September 2021 due to hypoxemic respiratory failure. A panel of 18 immune response biomarkers in the complement, coagulation and endothelial function domains were measured using ELISA or Luminex. Biomarkers were measured on day 0-1, day 2-4 and day 6-8 after start of COVID-19 treatment. Patients were categorized into four treatment groups: no immunomodulatory treatment, corticosteroids, anakinra plus corticosteroids, or tocilizumab plus corticosteroids. The association between treatment group and the change in concentrations of biomarkers was estimated with linear mixed-effects models, using no immunomodulatory treatment as reference group. 109 patients with a median age of 62 years [IQR 54-70] of whom 72% (n = 78) was male, were included in this analysis. Both anakinra plus corticosteroids (n = 22) and tocilizumab plus corticosteroids (n = 38) were associated with an increase in angiopoietin-1 compared to no immune modulator (n = 23) (beta of 0.033 [0.002-0.064] and 0.041 [0.013-0.070] per day, respectively). These treatments, as well as corticosteroids alone (n = 26), were further associated with a decrease in the ratio of angiopoietin-2/angiopoietin-1 (beta of 0.071 [0.034-0.107], 0.060 [0.030-0.091] and 0.043 [0.001-0.085] per day, respectively). Anakinra plus corticosteroids and tocilizumab plus corticosteroids were associated with a decrease in concentrations of complement complex 5b-9 compared to no immunomodulatory treatment (0.038 [0.006-0.071] and 0.023 [0.000-0.047], respectively). Currently established treatments for critically ill COVID-19 patients are associated with a change in biomarkers of the angiopoietin and complement pathways, possibly indicating a role for stability of the endothelium. These results increase the understanding of the mechanisms of interventions and are possibly useful for stratification of patients with other inflammatory conditions which may potentially benefit from these treatments.

Effects of robotic-assisted early mobilization versus conventional mobilization in intensive care unit patients: prospective interventional cohort study with retrospective control group analysis.

BACKGROUND: Approximately one in three survivors of critical illness suffers from intensive-care-unit-acquired weakness, which increases mortality and impairs quality of life. By counteracting immobilization, a known risk factor, active mobilization may mitigate its negative effects on patients. In this single-center trial, the effect of robotic-assisted early mobilization in the intensive care unit (ICU) on patients' outcomes was investigated. METHODS: We enrolled 16 adults scheduled for lung transplantation to receive 20 min of robotic-assisted mobilization and verticalization twice daily during their first week in the ICU (intervention group: IG). A control group (CG) of 13 conventionally mobilized patients after lung transplantation was recruited retrospectively. Outcome measures included the duration of mechanical ventilation, length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months. RESULTS: During the first week in the ICU, the intervention group received a median of 6 (interquartile range 3-8) robotic-assisted sessions of early mobilization and verticalization. There were no statistically significant differences in the duration of mechanical ventilation (IG: median 126 vs. CG: 78 h), length of ICU stay, muscle parameters evaluated by ultrasound, and quality of life after three months between the IG and CG. CONCLUSION: In this study, robotic-assisted mobilization was successfully implemented in the ICU setting. No significant differences in patients' outcomes were observed between conventional and robotic-assisted mobilization. However, randomized and larger studies are necessary to validate the adequacy of robotic mobilization in other cohorts. TRIAL REGISTRATION: This single-center interventional trial was registered in clinicaltrials.gov as NCT05071248 on 27/08/2021.

Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis.

PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

The Effect of Albumin Administration in Critically Ill Patients: A Retrospective Single-Center Analysis.

OBJECTIVES: The aim of this study was to analyze the development of albumin administration in patients admitted to the adult ICU. In addition, we assessed the impact of albumin administration on serum hemoglobin concentration. DESIGN: We conducted a retrospective single-center study including all patients who were admitted to the ICU from January 2013 to December 2021 and stayed at least 24 hours. SETTING: The study was conducted in an academic hospital (University Hospital Basel, Switzerland). PATIENTS: A total of 20,927 admissions were included, of which 3748 received albumin at least once during their ICU stay. To analyze volume expansion, 2006 admissions met the inclusion criteria, namely at least two hemoglobin measurements within 12 hours, one albumin delivery, and experienced no bleeding, dialysis, or transfusions during this period. INTERVENTIONS: None. MEASUREMENTS: We examined the hemoglobin levels before and after albumin administration and compared them with a matched control group to assess the amount and duration of volume expansion. MAIN RESULTS: From 2013 to 2021 the proportion of critically ill patients treated with albumin rose from 5.0% to 32.5%. An overproportioned increase in albumin use could be seen in surgical patients (4.7-47.2%) and in those receiving RBC transfusion (13.7-72.6%). In those patients receiving albumin, a significant drop in hemoglobin of around 5 g/L on average could be observed following treatment with albumin. CONCLUSION: Hemodilution was observable for at least 12 hours after albumin administration and may have caused a decrease in hemoglobin concentration of greater than 8 g/L when isooncotic albumin solution (5%, 25 g in 500 mL) was administered. This makes albumin, especially in its isooncotic form, an ideal colloid to achieve long-lasting volume expansion. However, RBC transfusions may increase under albumin therapy, as transfusion thresholds may be undershot after albumin administration.

Risk prediction for severe COVID-19 progressing to critical illness and death in the ICU and efficacy analysis of using traditional Chinese medicine.

To reveal the key factors influencing the progression of severe COVID-19 to critical illness and death in the intensive care unit (ICU) and to accurately predict the risk, as well as to validate the efficacy of treatment using traditional Chinese medicine (TCM), thus providing valuable recommendations for the clinical management of patients. A total of 189 patients with COVID-19 in 25 ICUs in Chongqing, China, were enrolled, and 16 eventually died. Statistical models shown that factors influencing the progression of COVID-19 to critical illness include the severity of illness at diagnosis, the mode of respiratory support, and the use of TCM. Risk factors for death include a history of metabolic disease, the use of antiviral drugs and TCM, and invasive endotracheal intubation. The area under curve of the noncollinearity model predicted the risk of progression to critical illness and the risk of death reached 0.847 and 0.876, respectively. The use of TCM is an independent protective factor for the prevention of the progression of severe COVID-19, while uncorrectable hypoxemia and invasive respiratory support are independent risk factors, and antiviral drugs can help reduce mortality. The multifactorial prediction model can assess the risk of critical illness and death in ICU COVID-19 patients, and inform clinicians in choosing the treatment options and medications.

The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. METHODS: Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). RESULTS: There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). CONCLUSION: This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.

Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials.

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.

Clinical outcomes of colistin methanesulfonate sodium in correlation with pharmacokinetic parameters in critically ill patients with multi-drug resistant bacteria-mediated infection: A systematic review and meta-analysis.

BACKGROUND: Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and nephrotoxicity risks hinder its clinical use. Thus, the aim of this study is to investigate clinical outcomes in correlation with pharmacokinetic differences and infection types in critically ill patients on intravenous colistin methanesulfornate sodium (CMS). METHODS: A systematic literature search of Embase, Google Scholars, and PubMed was performed to identify clinical trials evaluating pharmacokinetic parameters along with clinical outcomes of CMS treatment from inception to July 2023. The pooled analyses of clinical impact of CMS on nephrotoxicity, mortality, clinical cure, and colistin concentration at steady state (Css,avg) were performed. This study was registered in the PROSPERO (CRD 42023456120). RESULTS: Total of 695 critically ill patients from 17 studies were included. The mortality was substantially lower in clinically cured patients (OR 0.05; 95% CI 0.02 - 0.14), whereas the mortality rate was statistically insignificant between nephrotoxic and non-nephrotoxic patients. Inter-patient variability of pharmacokinetic parameters of CMS and colistin was observed in critically ill patients. The standard mean differences of Css,avg were statistically insignificant between clinically cure and clinically failure groups (standard mean difference (SMD) -0.25; 95% CI -0.69 - 0.19) and between nephrotoxic and non-nephrotoxic groups (SMD 0.67; 95% CI -0.27-1.61). The clinical cure rate is substantially lower in pneumonia patients (OR 0.09; 95% CI 0.01 - 0.56), and pharmacokinetic parameters pertaining to microbiological cure were different among strains. CONCLUSION: The mortality rate was substantially lower in clinically cured patients with CMS. However, no significant differences in Css,avg of colistin were examined to determine the impact of pharmacokinetic differences on clinical outcomes including mortality rate and nephrotoxicity risk. Nevertheless, the clinical cure rate is substantially lower in patients with respiratory infection than patients with urinary tract infection.

Baseline immune status and the effectiveness of response to enteral nutrition among ICU patients with COVID-19: An observational, retrospective study.

OBJECTIVES: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes. METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients. RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients. CONCLUSION: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients' immunity status.

[Parenteral nutrition : choosing the adequate vascular access]. / 5 minutes pour apprendre. Nutrition parentérale : choisir l'accès vasculaire adéquat.

Malnutrition is a common condition among hospitalized patients and has an important impact on morbidity and mortality. Despite enteral nutrition being the preferred option for patients requiring artificial alimentation, parenteral nutrition (PN) can be required. This article emphasizes the importance of choosing the adequate vascular access based on the chosen PN. Furthermore, it reviews indications, contraindications and complications of PN.

Long-term, patient-centered, frailty-based outcomes of older critical illness survivors from the emergency department: a post hoc analysis of the LIFE Study.

BACKGROUND: Evidence indicates frailty before intensive care unit (ICU) admission leads to poor outcomes. However, it is unclear whether quality of life (QOL) and activities of daily living (ADL) for survivors of critical illness admitted to the ICU via the emergency department remain consistent or deteriorate in the long-term compared to baseline. This study aimed to evaluate long-term QOL/ADL outcomes in these patients, categorized by the presence or absence of frailty according to Clinical Frailty Scale (CFS) score, as well as explore factors that influence these outcomes. METHODS: This was a post-hoc analysis of a prospective, multicenter, observational study conducted across Japan. It included survivors aged 65 years or older who were admitted to the ICU through the emergency department. Based on CFS scores, participants were categorized into either the not frail group or the frail group, using a threshold CFS score of < 4. Our primary outcome was patient-centered outcomes (QOL/ADL) measured by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and the Barthel Index six months post-ICU admission, comparing results from baseline. Secondary outcomes included exploration of factors associated with QOL/ADL six months post-ICU admission using multiple linear regression analyses. RESULTS: Of 514 candidates, 390 participants responded to the EQ-5D-5L questionnaire, while 237 responded to the Barthel Index. At six months post-admission, mean EQ-5D-5L values declined in both the not frail and frail groups (0.80 to 0.73, p = 0.003 and 0.58 to 0.50, p = 0.002, respectively); Barthel Index scores also declined in both groups (98 to 83, p < 0.001 and 79 to 61, p < 0.001, respectively). Multiple linear regression analysis revealed that baseline frailty (ß coefficient, -0.15; 95% CI, - 0.23 to - 0.07; p < 0.001) and pre-admission EQ-5D-5L scores (ß coefficient, 0.14; 95% CI, 0.02 to 0.26; p = 0.016) affected EQ-5D-5L scores at six months. Similarly, baseline frailty (ß coefficient, -12.3; 95% CI, - 23.9 to - 0.80; p = 0.036) and Barthel Index scores (ß coefficient, 0.54; 95% CI, 0.30 to 0.79; p < 0.001) influenced the Barthel Index score at six months. CONCLUSIONS: Regardless of frailty, older ICU survivors from the emergency department were more likely to experience reduced QOL and ADL six months after ICU admission compared to baseline.