Journal of Intensive Care最新文献

Background: Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes.

Methods: This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80-120%), and the upper group (> 120%).

Results: The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups.

Conclusions: Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients.

Trial registration: Not applicable.

Objectives: This review examined studies regarding the implementation and translation of patients' advance directives (AD) in intensive care units (ICUs), focusing on practical difficulties and obstacles.

Methods: The digital PubMed and Medline databases were screened using predefined keywords to identify relevant prospective and retrospective studies published until 2022.

Results: Seventeen studies from the United States, Europe, and South Africa (including 149,413 patients and 1210 healthcare professionals) were identified. The highest prevalence of ADs was described in a prospective study in North America (49%), followed by Central Europe (13%), Asia (4%), Australia and New Zealand (4%), Latin America (3%), and Northern and Southern Europe (2.6%). While four retrospective studies reported limited effects of ADs, four retrospective studies, one survey and one systematic review indicated significant effects on provision of intensive care, higher rates of do-not-resuscitate orders, and care withholding in patients with ADs. Four of these studies showed shorter ICU stays, and lower treatment costs in patients with ADs. One prospective and two retrospective studies reported issues with loss, delayed or no transmission of ADs. One survey revealed that 91% of healthcare workers did not regularly check for ADs. Two retrospective studies and two survey revealed that the implementation of directives is further challenged by issues with their applicability, phrasing, and compliance by the critical care team and family members.

Conclusions: Although ADs may improve intensive- and end-of-life care, insufficient knowledge, lack of awareness, poor communication between healthcare providers and patients or surrogates, lack of standardization of directives, as well as ethical and legal concerns challenge their implementation.

Background: The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU).

Methods: This was a multicenter, randomized, double-blinded, fentanyl-controlled, non-inferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl: 0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score [NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard procedures. PK of remifentanil in the arterial blood was assessed in 24 patients.

Results: The proportion of patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8% (88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, - 0.8-5.3) and non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%), respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%), respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of the end of administration, suggesting rapid offset of action following discontinuation of remifentanil.

Conclusions: Remifentanil can be used safely for pain management in mechanically ventilated Japanese patients in the ICU.

Trial registration: Japan Registry of Clinical Trials, jRCT2080224954. Registered 20 November 2019, https://jrct.niph.go.jp/latest-detail/jRCT2080224954 .

Background: This study aimed to apply the backpropagation neural network (BPNN) to develop a model for predicting multidrug-resistant organism (MDRO) infection in critically ill patients.

Methods: This study collected patient information admitted to the intensive care unit (ICU) of the Affiliated Hospital of Qingdao University from August 2021 to January 2022. All patients enrolled were divided randomly into a training set (80%) and a test set (20%). The least absolute shrinkage and selection operator and stepwise regression analysis were used to determine the independent risk factors for MDRO infection. A BPNN model was constructed based on these factors. Then, we externally validated this model in patients from May 2022 to July 2022 over the same center. The model performance was evaluated by the calibration curve, the area under the curve (AUC), sensitivity, specificity, and accuracy.

Results: In the primary cohort, 688 patients were enrolled, including 109 (15.84%) MDRO infection patients. Risk factors for MDRO infection, as determined by the primary cohort, included length of hospitalization, length of ICU stay, long-term bed rest, antibiotics use before ICU, acute physiology and chronic health evaluation II, invasive operation before ICU, quantity of antibiotics, chronic lung disease, and hypoproteinemia. There were 238 patients in the validation set, including 31 (13.03%) MDRO infection patients. This BPNN model yielded good calibration. The AUC of the training set, the test set and the validation set were 0.889 (95% CI 0.852-0.925), 0.919 (95% CI 0.856-0.983), and 0.811 (95% CI 0.731-0.891), respectively.

Conclusions: This study confirmed nine independent risk factors for MDRO infection. The BPNN model performed well and was potentially used to predict MDRO infection in ICU patients.

Background: Lacosamide is one of the anticonvulsants used in critically ill patients. This study aimed to suggest appropriate lacosamide dosing regimens in critically ill patients receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulations.

Methods: Mathematical models were created using published demographic and pharmacokinetics in adult critically ill patients. CRRT modalities with different effluent rates were added into the models. Lacosamide regimens were evaluated on the probability of target attainment (PTA) using pharmacodynamic targets of trough concentrations and area under the curve within a range of 5-10 mg/L and 80.25-143 and 143-231 mg*h/L for the initial 72 h-therapy, respectively. Optimal regimens were defined from regimens that yielded the highest PTA. Each dosing regimen was tested in a group of different 10,000 virtual patients.

Results: Our results revealed the optimal lacosamide dosing regimen of 300-450 mg/day is recommended for adult patients receiving both CRRT modalities with 20-25 effluent rates. The dose of 600 mg/day was suggested in higher effluent rate of 35 mL/kg/h. Moreover, a patient with body weight > 100 kg was less likely to attain the targets.

Conclusions: Volume of distribution, total clearance, CRRT clearance and body weight were significantly contributed to lacosamide dosing. Clinical validation of the finding is strongly indicated.

Background: The efficacy of therapeutic drug monitoring (TDM)-based antimicrobial dosing optimization strategies on pharmacokinetics/pharmacodynamics and specific drug properties for critically ill patients is unclear. Here, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of TDM-based regimen in these patients.

Methods: Articles from three databases were systematically retrieved to identify relevant randomized control studies. Version two of the Cochrane tool for assessing risk of bias in randomized trials was used to assess the risk of bias in studies included in the analysis, and quality assessment of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Primary outcome was the 28-day mortality and secondary outcome were in-hospital mortality, clinical cure, length of stay in the intensive care unit (ICU) and target attainment at day 1 and 3.

Results: In total, 5 studies involving 1011 patients were included for meta-analysis of the primary outcome, of which no significant difference was observed between TDM-based regimen and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.77-1.14; I² = 0%). In-hospital mortality (RR 0.96, 95% CI: 0.76-1.20), clinical cure (RR 1.23, 95% CI: 0.91-1.67), length of stay in the ICU (mean difference 0, 95% CI: - 2.18-2.19), and target attainment at day 1 (RR 1.14, 95% CI: 0.88-1.48) and day 3 (RR 1.35, 95% CI: 0.90-2.03) were not significantly different between the two groups, and all evidence for the secondary outcomes had a low or very low level of certainty because the included studies had serious risk of bias, variation of definition for outcomes, and small sample sizes.

Conclusion: TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required.

Trial registration: Clinical trial registration; PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), registry number: CRD 42022371959. Registered 24 November 2022.

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions.