Liberation from Mechanical Ventilation in Critically Ill Patients: Korean Society of Critical Care Medicine Clinical Practice Guidelines.

BACKGROUND: Successful liberation from mechanical ventilation is one of the most crucial processes in critical care because it is the first step by which a respiratory failure patient begins to transition out of the intensive care unit and return to their own life. Therefore, when devising appropriate strategies for removing mechanical ventilation, it is essential to consider not only the individual experiences of healthcare professionals, but also scientific and systematic approaches. Recently, numerous studies have investigated methods and tools for identifying when mechanically ventilated patients are ready to breathe on their own. The Korean Society of Critical Care Medicine therefore provides these recommendations to clinicians about liberation from the ventilator. METHOD: Meta-analyses and comprehensive syntheses were used to thoroughly review, compile, and summarize the complete body of relevant evidence. All studies were meticulously assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method, and the outcomes were presented succinctly as evidence profiles. Those evidence syntheses were discussed by a multidisciplinary committee of experts in mechanical ventilation, who then developed and approved recommendations. RESULT: Recommendations for nine population, intervention, comparator, outcome (PICO) questions about ventilator liberation are presented in this document. This guideline includes seven conditional recommendations, one expert consensus recommendation, and one conditional deferred recommendation. CONCLUSIONS: We developed these clinical guidelines for mechanical ventilation liberation to provide meaningful recommendations. These guidelines reflect the best treatment for patients seeking liberation from mechanical ventilation.

Physico-chemical characterization of acid base disorders in patients with COVID-19: A cohort study.

BACKGROUND: Acid-base imbalance has been poorly described in patients with coronavirus disease 2019 (COVID-19). Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been overlooked using traditional acid-base analysis techniques. In a cohort of critically ill COVID-19 patients, we looked for an association between metabolic acidosis surrogates and worse clinical outcomes, such as mortality, renal dialysis, and length of hospital stay. AIM: To describe the acid-base disorders of critically ill COVID-19 patients using Stewart's approach, associating its variables with poor outcomes. METHODS: This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan. Laboratory and clinical data were obtained from electronic records. Categorical variables were compared using Fisher's exact test. Continuous data were presented as median and interquartile range. The Mann-Whitney U test was used for comparisons. RESULTS: In total, 211 patients were analyzed. The mortality rate was 13.7%. Overall, 149 patients (70.6%) presented with alkalosis, 28 patients (13.3%) had acidosis, and the remaining 34 patients (16.2%) had a normal arterial pondus hydrogenii. Of those presenting with acidosis, most had a low apparent strong ion difference (SID) (20 patients, 9.5%). Within the group with alkalosis, 128 patients (61.0%) had respiratory origin. The non-survivors were older, had more comorbidities, and had higher Charlson's and simplified acute physiology score 3. We did not find severe acid-base imbalance in this population. The analyzed Stewart's variables (effective SID, apparent SID, and strong ion gap and the effect of albumin, lactate, phosphorus, and chloride) were not different between the groups. CONCLUSION: Alkalemia is prevalent in COVID-19 patients. Although we did not find an association between acid-base variables and mortality, the use of Stewart's methodology may provide insights into this severe disease.

Calibration trial of an innovative medical device (NEVVA© ) for the evaluation of pain in non-communicating patients in the intensive care unit.

Background: Pain management is an essential and complex issue for non-communicative patients undergoing sedation in the intensive care unit (ICU). The Behavioral Pain Scale (BPS), although not perfect for assessing behavioral pain, is the gold standard based partly on clinical facial expression. NEVVA© , an automatic pain assessment tool based on facial expressions in critically ill patients, is a much-needed innovative medical device. Methods: In this prospective pilot study, we recorded the facial expressions of critically ill patients in the medical ICU of Caen University Hospital using the iPhone and Smart Motion Tracking System (SMTS) software with the Facial Action Coding System (FACS) to measure human facial expressions metrically during sedation weaning. Analyses were recorded continuously, and BPS scores were collected hourly over two 8 h periods per day for 3 consecutive days. For this first stage, calibration of the innovative NEVVA© medical device algorithm was obtained by comparison with the reference pain scale (BPS). Results: Thirty participants were enrolled between March and July 2022. To assess the acute severity of illness, the Sequential Organ Failure Assessment (SOFA) and the Simplified Acute Physiology Score (SAPS II) were recorded on ICU admission and were 9 and 47, respectively. All participants had deep sedation, assessed by a Richmond Agitation and Sedation scale (RASS) score of less than or equal to -4 at the time of inclusion. One thousand and six BPS recordings were obtained, and 130 recordings were retained for final calibration: 108 BPS recordings corresponding to the absence of pain and 22 BPS recordings corresponding to the presence of pain. Due to the small size of the dataset, a leave-one-subject-out cross-validation (LOSO-CV) strategy was performed, and the training results obtained the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.792. This model has a sensitivity of 81.8% and a specificity of 72.2%. Conclusion: This pilot study calibrated the NEVVA© medical device and showed the feasibility of continuous facial expression analysis for pain monitoring in ICU patients. The next step will be to correlate this device with the BPS scale.

From the Intensive Care Unit to Recovery: Managing Post-intensive Care Syndrome in Critically Ill Patients.

Post-intensive care syndrome (PICS) is the term used to describe the decline in the physical, cognitive, and/or mental condition of individuals who have been discharged from the intensive care unit (ICU). This complication could result in a significant reduction in quality of life, with some patients experiencing symptoms of prolonged weakness, depression, anxiety, and post-traumatic stress disorder (PTSD). Intensive care advancement over the years has resulted in an increase in ICU survival rates and a proportional increase in PICS, creating a need for more in-depth research into the prevention and management of the disease. Hence, this study aims to examine the present body of literature on PICS, encompassing its underlying physiological processes and elements that contribute to its development, methods for evaluating and diagnosing the condition, current treatment choices as well as potential new approaches, and the constraints in managing PICS and the necessity for further investigation. In this article, studies were compiled from several databases, including, but not limited to, Google Scholar, PubMed, and Cochrane Library. These studies were reviewed, and their data were used to highlight important aspects regarding the efficacy of current PICS screening tools, the optimization and limitations of both pharmacologic and non-pharmacologic treatment methods, and the feasibility and safety of emerging treatments and technologies. The major conclusions of this review were centered around the need for multidisciplinary management of PICS. From pharmacological management using analgesia to non-pharmacological management using early mobilization and exercise therapy, the effective treatment of PICS requires a multifaceted approach. Patient follow-up and its importance were touched upon, including strategies and policies to bolster proper follow-up, thereby increasing favorable outcomes. Lastly, the importance of family involvement and the increased need for research into this topic were highlighted.

Nurses' perceptions of patient pain, delirium, and sedation assessments in the intensive care unit: A qualitative study.

BACKGROUND: Pain, delirium, and sedation should be assessed routinely using validated assessment scales. Inappropriately managed pain, delirium, and sedation in critically ill patients can have serious consequences regarding mortality, morbidity, and increased healthcare costs. Despite the benefits of a bundled approach to pain, delirium, and sedation assessments, few studies have explored nurses' perceptions of using validated scales for such assessments. Furthermore, no studies have examined nurses' perceptions of undertaking these assessments as a bundled approach. OBJECTIVES: The objective of this study was to explore nurses' knowledge, perceptions, attitudes, and experiences regarding the use of validated pain, delirium, and sedation assessment tools as a bundled approach in the intensive care unit (ICU). METHODS: A qualitative exploratory descriptive design was adopted. We conducted four focus groups and 10 individual interviews with 23 nurses from a 26-bed adult ICU at an Australian metropolitan tertiary teaching hospital. Data were analysed using thematic analysis techniques. FINDINGS: Four themes were identified: (i) factors impacting nurses' ability to undertake pain, delirium, and sedation assessments in the ICU; (ii) use, misuse, and nonuse of tools and use of alternative strategies to assess pain, delirium, and sedation; (iii) implementing assessment tools; and (iv) consequences of suboptimal pain, delirium, and sedation assessments. A gap was found in nurses' use of validated scales to assess pain, delirium, and sedation as a bundled approach, and they were not familiar with using a bundled approach to assessment. CONCLUSION: The practice gap could be addressed using a carefully planned implementation strategy. Strategies could include a policy and protocol for assessing pain, delirium, and sedation in the ICU, engagement of change champions to facilitate uptake of the strategy, reminder and feedback systems, further in-service education, and ongoing workplace training for nurses.

Role of neuromuscular blocking agents in the development of polyneuropathy and myopathy in critically ill patients. / Rol de los bloqueantes neuromusculares en el desarrollo de polineuropatía y miopatía del enfermo crítico.

BACKGROUND: Acquired critical illness weakness (AWCIP) is the most frequent neuromuscular disease in intensive care medicine departments. Its importance is given by the prolongation of hospital stay and the delayed recovery it causes to patients after hospitalization. The main objective of this study was to investigate the association between neuromuscular blocking agents and the development of acquired weakness in critically ill patients. MATERIAL AND METHODS: We conducted a prospective study of 103 critically ill patients who were periodically monitored with electromyography. RESULTS: The development of AWCIP was observed in 63 patients. The group of patients who developed AWCIP had a significantly higher utilization of neuromuscular blocking agents than the group who did not develop AWCIP [79.4% vs 50%, OR:3.85 (1.63-9.39), p <0.02]; likewise, this group of patients had a longer ICU stay [32 days vs 14 days, OR: 1.11 (1.06-1.17), p <0. 001] and a longer mechanical ventilation time [24 days vs 9 days, OR:1.2 (1.11-1.32), p <0.001]. CONCLUSION: Neuromuscular blocking agents are a factor associated with the occurrence of AWCIP.

Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Antibiotic Exposure of Critically Ill Children at a Tertiary Care Paediatric Intensive Care Unit in Switzerland.

Antibiotic overtreatment fosters multidrug-resistance that threatens healthcare systems worldwide as it increases patient morbidity and mortality. Contemporary data on antibiotic usage on tertiary care paediatric intensive care units for in- and external benchmarking are scarce. This was a single-centre retrospective quality control study including all patients with antibiotic treatment during their hospitalization at a paediatric intensive care unit in the time period 2019-2021. Antibiotic treatment was calculated as days of therapy (DOT) per 100 patient days (DOT/100pd). Further, the variables PIM II score, length of stay in intensive care (LOS), gender, age, treatment year, reason for intensive care unit admission, and death were assessed. Two thousand and forty-one cases with a median age of 10 months [IQR 0-64] were included; 53.4% were male, and 4.5% of the included patients died. Median LOS was 2.73 days [0.07-5.90], and PIM II score was 1.98% [0.02-4.86]. Overall, the antibiotic exposure of critically ill children and adolescents was 59.8 DOT/100pd. During the study period, the antibiotic usage continuously increased (2019: 55.2 DOT/100pd; 2020: 59.8 DOT/100pd (+8.2%); 2021: 64.5 DOT/100pd (+8.0%)). The highest antibiotic exposure was found in the youngest patients (0-1 month old (72.7 DOT/100pd)), in patients who had a LOS of >2-7 days (65.1 DOT/100pd), those who had a renal diagnosis (98 DOT/100pd), and in case of death (91.5 DOT/100pd). Critically ill paediatric patients were moderately exposed to antibiotics compared to data from the previously published literature. The current underreporting of antimicrobial prescription data in this cohort calls for future studies for better internal and external benchmarking.

Impact of early high protein intake in critically ill patients: a randomized controlled trial.

BACKGROUND: Conflicting findings regarding the impact of High protein intake during the early phase in critically ill patients have been reported. Therefore, we aimed to assess the influence of higher early protein intake on the prognosis of critically ill patients. METHODS: This randomized controlled trial involved 173 critically ill patients who stayed in the Intensive Care Unit/Emergency ICU (ICU/EICU) for at least 7 days. The Low group (n = 87) and High group (n = 86) received protein supplementation of 0.8 g/kg.d and 1.5 g/kg.d, respectively, within 1-3 days of enteral nutrition (EN) initiation, with both groups transitioning to 1.5 g/kg.d on the 4th day. The serum prealbumin (PA), blood urea nitrogen/creatinine, and rectus femoris muscle thickness and cross-sectional area of all patients was measured on the 1th, 3rd, 5th, 7th day, and the day of ICU/EICU discharge. RESULTS: Patients in both Low and High groups showed no significant differences in age, APACHE II scores, or other demographic and baseline characteristics. There were also no significant differences in the primary outcome (28-day mortality rate) and secondary outcomes (incidence rate of refeeding syndrome and EN tolerance score) between the two groups. However, the Low group exhibited a significantly higher 28-day mortality rate (HR = 2.462, 95% CI: 1.021-5.936, P = 0.045) compared to High group, as determined by Cox proportional hazards models incorporating the time factor. The High group exhibited significantly shorter durations of mechanical ventilation and ICU stay compared to the Low group. Serum PA levels were higher, and rectus femoris muscle atrophy rates were lower in the High group. Furthermore, for septic patients, high protein intake significantly reduced the 28-day mortality rate despite a small sample size (n = 34). CONCLUSIONS: Our study indicates that increasing early protein intake to 1.5 g/kg.d may be safe and help improve the nutritional status and prognosis of critically ill patients. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (ChiCTR2000039997, https://www.chictr.org.cn/ ).

Association between aspirin and mortality in critically ill patients with atrial fibrillation: a retrospective cohort study based on mimic-IV database.

Background: Atrial fibrillation (AF) is a prevalent issue among critically ill patients, and the availability of effective treatment strategies for AF is limited. Aim: The objective of this study was to evaluate the mortality rate associated with AF in critically ill patients who were either aspirin or non-aspirin users. Methods: This cohort study incorporated critically ill patients with AF from the Medical Information Mart for Intensive Care database. The study compared incidences of 28-day mortality, 90-day mortality, and 1-year mortality between patients with and without aspirin prescriptions. To assess the association between aspirin and the endpoints, Kaplan-Meier analysis and Cox proportional hazards regression analyses were conducted. Results: In this study, a total of 13,330 critically ill patients with atrial fibrillation (AF) were included, of which 4,421 and 8,909 patients were categorized as aspirin and non-aspirin users, respectively. The 28-day, 90-day, and 1-year mortality rates were found to be 17.5% (2,330/13,330), 23.9% (3,180/13,330), and 32.9% (4,379/13,330), respectively. The results of a fully-adjusted Cox proportional hazard model indicated that aspirin use was negatively associated with the risk of death after adjusting for confounding factors (28-day mortality, HR 0.64, 95% CI 0.55-0.74; 90-day mortality, HR 0.65, 95% CI 0.58-0.74; 1-year mortality, HR 0.67, 95%CI 0.6∼0.74). The results of the subgroup analysis indicate a more robust correlation, specifically among patients under the age of 65 and those without a history of congestive heart failure or myocardial infarction. Conclusions: The utilization of aspirin may exhibit a correlation with a reduction in risk-adjusted mortality from all causes in critically ill patients diagnosed with atrial fibrillation. However, additional randomized controlled trials are necessary to elucidate and confirm this potential association.

Status of knowledge, attitude and practice of clinical nurses towards the intrahospital transport of critically ill patients: A cross-sectional study.

AIMS: To explore the knowledge, attitudes and practice status of the intrahospital transport (IHT) of critically ill patients among clinical nurses and their influencing factors. DESIGN: Cross-sectional study. METHODS: A questionnaire determined the nurses' knowledge, attitudes and practice scores. The questionnaire was used for data collection in a tertiary hospital from 10 January to 17 January 2023. Multivariate regression analysis was also used to evaluate the related factors of IHT of critically ill patients in different dimensions. RESULTS: Out of 670 distributed questionnaires, 612 nurses returned the completed questionnaire. The scores of KAP were (9.72 ± 1.61), (42.91 ± 4.58) and (82.84 ± 1.61), respectively. Pearson's correlation analysis showed that knowledge, attitude and behaviour scores were positively correlated. Variables that were associated with the scores of transfer knowledge were the scores of transfer practice, different departments and the scores of transfer attitude. The score of practice, number of IHT and received hospital-level training had statistical significance on the nurses' attitude scores. Furthermore, the score of the attitude and transport knowledge had statistical significance on the nurses' practice. CONCLUSION: The findings indicate a clear need for clinical nurses' knowledge of IHT of critically ill patients, especially in the emergency department (ED) and ICU. In addition, nurses need to be more active in transporting critically ill patients. Managers should enhance nurses' confidence in the IHT of critically ill patients and promote clinical nurses to establish a correct and positive attitude. IMPACT: The findings of this study benefit nursing managers in understanding the current situation of IHT of critically ill patients. Managers should apply new training methods to nursing education and develop a multi-level training program that is systematic, comprehensive and demand-oriented. PATIENT OR PUBLIC CONTRIBUTION: The participants of this study were nurses and this contribution has been explained in the Data collection section. There was no patient contribution in this study.

Mortality Prediction by Kinetic Parameters of Lactate and S-Adenosylhomocysteine in a Cohort of Critically Ill Patients.

Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.

Acute Gastrointestinal Injury in Critically Ill Patients in a South Indian Intensive Care Unit: A Prospective, Observational, Preliminary Study.

Introduction The acute gastrointestinal injury (AGI) score was proposed by the Working Group on Abdominal Problems of the European Society of Intensive Care Medicine (ESICM) as a tool to define and grade gut dysfunction. There have not been any studies in India to validate this tool. The objective of this preliminary study was primarily to study the frequency of AGI in the first week of ICU stay in critically ill patients in our intensive care unit (ICU). We also sought to determine the risk factors predisposing to the development of AGI and to determine the prognostic implication of gastrointestinal (GI) injury in critically ill patients. Materials and methods A prospective, observational, preliminary, single-center study was conducted on critically ill patients (APACHE II > 8) who were on enteral tube feeds and admitted to a mixed ICU of a tertiary care hospital. Anthropometric data, admission diagnosis, APACHE II score, and comorbidities were recorded. Data of daily heart rate, mean arterial pressure, dose of vasopressors, intra-abdominal pressure, fluid balance, feeding intolerance, mechanical ventilation, and laboratory tests were noted for the first seven days of ICU stay or till ICU discharge, whichever was earlier. The occurrence of AGI score (1-4) during the first seven days of critical illness was the primary outcome of interest. Patient outcome at 28 days was recorded and the impact of the occurrence of AGI on patient outcome was analyzed using the Chi-square test. The patient characteristics associated with AGI were characterized as risk factors and analyzed using a multivariate model. Results Data were collected from 33 patients over 201 patient days. The frequency of acute GI dysfunction in the first seven days of ICU stay in our group of patients was 45.45% (15/33). APACHE II, fluid balance, creatinine, and lactate were identified as possible predictors of GI injury based on existing literature. These four variables were entered into an ordinal logistic regression model to assess their ability to predict the occurrence of GI Injury. When fitted into a predictive model, only fluid balance and creatinine were predictive of the final model (p-value < 0.05). A greater fluid balance was predictive in the final model of the development of GI injury; however, it showed negligible clinical significance (OR: 1.00033, 95% CI: 1.000051-1.00061). Lower creatinine levels were predictive in the final model of the development of AGI Injury, as demonstrated by the negative coefficient. Creatinine also had a greater clinical significance (OR: 0.63, 95% CI: 0.44-0.90) in the development of AGI. The impact of the AGI scores on mortality was analyzed. The number of patient days with higher AGI scores was significantly associated with increased mortality at 28 days (p-value < 0.001). Conclusion The study showed that nearly half of the critically ill patients included in the study developed acute GI dysfunction. We could not identify any predictors of GI injury based on our results. The result suggested an association between the severity of GI dysfunction and mortality at 28 days.

Comparison of Continuous Intracortical and Scalp Electroencephalography in Comatose Patients with Acute Brain Injury.

BACKGROUND: Depth electroencephalography (dEEG) is a recent invasive monitoring technique used in patients with acute brain injury. This study aimed to describe in detail the clinical manifestations of nonconvulsive seizures (NCSzs) with and without a surface EEG correlate, analyze their long-standing effects, and provide data that contribute to understanding the significance of certain scalp EEG patterns observed in critically ill patients. METHODS: We prospectively enrolled a cohort of 33 adults with severe acute brain injury admitted to the neurological intensive care unit. All of them underwent multimodal invasive monitoring, including dEEG. All patients were scanned on a 3T magnetic resonance imaging scanner at 6 months after hospital discharge, and mesial temporal atrophy (MTA) was calculated using a visual scale. RESULTS: In 21 (65.6%) of 32 study participants, highly epileptiform intracortical patterns were observed. A total of 11 (34.3%) patients had electrographic or electroclinical seizures in the dEEG, of whom 8 had both spontaneous and stimulus-induced (SI) seizures, and 3 patients had only spontaneous intracortical seizures. An unequivocal ictal scalp correlate was observed in only 3 (27.2%) of the 11 study participants. SI-NCSzs occurred during nursing care, medical procedures, and family visits. Subtle clinical manifestations, such as restlessness, purposeless stereotyped movements of the upper limbs, ventilation disturbances, jerks, head movements, hyperextension posturing, chewing, and oroalimentary automatisms, occurred during intracortical electroclinical seizures. MTA was detected in 18 (81.8%) of the 22 patients. There were no statistically significant differences between patients with MTA with and without seizures or status epilepticus. CONCLUSIONS: Most NCSzs in critically ill comatose patients remain undetectable on scalp EEG. SI-NCSzs frequently occur during nursing care, medical procedures, and family visits. Semiology of NCSzs included ictal minor signs and subtle symptoms, such as breathing pattern changes manifested as patient-ventilator dyssynchrony.

Implementation of Modern Therapeutic Drug Monitoring and Lipidomics Approaches in Clinical Practice: A Case Study with Colistin Treatment.

Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the identification of specific lipids and/or significant changes in their plasma levels in patients suffering from cancer, Alzheimer's disease, sepsis, and many other diseases and pathological conditions. Profiling of lipids and determination of their plasma concentrations could also be helpful in the case of drug therapy management, especially in combination with therapeutic drug monitoring (TDM). Here, for the first time, a combined approach based on the TDM of colistin, a last-resort antibiotic, and lipidomic profiling is presented in a case study of a critically ill male patient suffering from Pseudomonas aeruginosa-induced pneumonia. Implementation of innovative analytical approaches for TDM (online combination of capillary electrophoresis with tandem mass spectrometry, CZE-MS/MS) and lipidomics (liquid chromatography-tandem mass spectrometry, LC-MS/MS) was demonstrated. The CZE-MS/MS strategy confirmed the chosen colistin drug dosing regimen, leading to stable colistin concentrations in plasma samples. The determined colistin concentrations in plasma samples reached the required minimal inhibitory concentration of 1 µg/mL. The complex lipidomics approach led to monitoring 545 lipids in collected patient plasma samples during and after the therapy. Some changes in specific individual lipids were in good agreement with previous lipidomics studies dealing with sepsis. The presented case study represents a good starting point for identifying particular individual lipids that could correlate with antimicrobial and inflammation therapeutic management.

Bilirubin influences the predictive effect of body mass index on hospital mortality in critically ill patients.

Introduction: Body mass index (BMI) can predict mortality in critically ill patients. Moreover, mortality is related to increased bilirubin levels. Thus, herein, we aimed to investigate the effect of bilirubin levels on the usefulness of BMI in predicting mortality in critically ill patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC IV) database. Patients were divided into two groups according to their total bilirubin levels within 24 h. Cox proportional hazard regression models were applied to obtain adjusted hazard ratios and 95 % confidence intervals for the correlation between BMI categories and hospital mortality. The dose-response relationship was flexibly modeled using a restricted cubic spline (RCS) with three knots. Results: Of the 14376 patients included, 3.4 % were underweight, 29.3 % were of normal body weight, 32.2 % were overweight, and 35.1 % were obese. For patients with total bilirubin levels <2 mg/dL, hospital mortality was significantly lower in patients with obesity than in normal body weight patients (p < 0.05). However, the opposite results were observed for patients with total bilirubin levels ≥2 mg/dL. The Cox proportional hazard regression models suggested that the risk of death was lower in patients with overweightness and obesity than in normal body weight patients when the total bilirubin levels were <2 mg/dL, but not in the other case (total bilirubin levels ≥2 mg/dL). RCS analyses showed that, for patients with total bilirubin levels <2 mg/dL, the risk of death gradually decreased with increasing BMI. Conversely, for patients with total bilirubin levels ≥2 mg/dL, this risk did not decrease with increasing BMI until reaching obesity, after which it increased rapidly. Conclusion: BMI predicted the risk of death differently in critically ill patients with different bilirubin levels.

Comparing BIS Monitoring vs. Clinical Assessment for Deep Sedation in the ICU: Effects on Delirium Reduction and Sedative Drug Doses - A randomized trial.

BACKGROUND: Sedative overdoses pose a delirium risk among Intensive Care Unit (ICU) patients, with potential mitigation through the use of a processed EEG monitor (BIS) to guide depth of sedation. RESEARCH QUESTION: Can BIS-guided deep sedation (RASS -4, -5) reduce sedative dosage and increase delirium-free and coma-free (DFCF) days? STUDY DESIGN AND METHODS: A randomized controlled trial was conducted in a tertiary mixed ICU, enrolling patients requiring deep sedation for >8 hours. Patients were randomly assigned to either the Clinical Assessment (CA) or BIS groups (BIS range of 40-60). Both groups utilized a BIS sensor, while the CA group's screen remained covered. After deep sedation, BIS sensors were removed, and delirium was assessed twice daily by researchers blinded to the randomization. The primary outcome was the number of DFCF days within 14 days after deep sedation. Additionally, we compared doses of sedative drugs and BIS values during deep sedation. RESULTS: Ninety-nine patients were included in the study. We found no significant difference in DFCF (p=0.1) between CA and BIS arms, but propofol doses were significantly lower in the BIS group (CA group 1.77 mg/kg/hr [95% CI 1.60, 1.93] vs. BIS group 1.44 mg/kg/hr [95% CI 1.04, 1.83]; p=0.03). During deep sedation, the CA group spent 46% of the total hours (95% CI 35, 57%) with BIS values below 40, whereas the BIS group spent 32% (95% CI 25, 40%), (p=0.03). Subgroup analysis focusing on patients sedated for more than 24 hours revealed an increase in DFCF in the BIS group (CA group median of 1 day [IQR 0, 9] vs. BIS group 8 days [IQR 0, 13]; p=0.04). INTERPRETATION: BIS-guided deep sedation did not improve DFCF days but reduced sedative drug use. In patients requiring sedation for more than 24 hours, it showed an improvement in DFCF days.

The New Delhi metallo-ß-lactamase-1 biosensor rapidly and accurately detected antibiotic plasma concentrations in cefuroxime-treated patients.

OBJECTIVES: Therapeutic drug monitoring (TDM) of ß-lactam antibiotics in critically ill patients may benefit dose optimisation, thus improving therapeutic outcomes. However, rapidly and accurately detecting these antibiotics in blood remains a challenge. This research group recently developed a thermometric biosensor called the New Delhi metallo-ß-lactamase-1 (NDM-1) biosensor, which detects multiple classes of ß-lactam antibiotics in spiked plasma samples. METHODS: This study assessed the NDM-1 biosensor's effectiveness in detecting plasma concentrations of ß-lactam antibiotics in treated patients. Seven patients receiving cefuroxime were studied. Plasma samples collected pre- and post-antibiotic treatment were analysed using the NDM-1 biosensor and compared with liquid chromatography coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The biosensor detected plasma samples without dilution, and a brief pre-treatment using a polyvinylidene fluoride filter significantly lowered matrix effects, reducing the running time to 5-8 minutes per sample. The assay's linear range for cefuroxime (6.25-200 mg/L) covered target concentrations during the trough phase of pharmacokinetics in critically ill patients. The pharmacokinetic properties of cefuroxime in treated patients determined by the NDM-1 biosensor and the UPLC-MS/MS were comparable, and the cefuroxime plasma concentrations measured by the two methods showed statistically good consistency. CONCLUSION: These data demonstrate that the NDM-1 biosensor assay is a fast, sensitive, and accurate method for detecting cefuroxime plasma concentrations in treated patients and highlights the NDM-1 biosensor as a promising tool for on-site TDM of ß-lactam antibiotics in critically ill patients.

miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Therapeutic plasma exchange combined with ribavirin to rescue critical SFTS patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS. METHODS: A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non-TPE group). Clinical and laboratory parameters were analyzed retrospectively. RESULTS: The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme-MB, prothrombin time, activated partial thromboplastin time, D-Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non-TPE group (P = 0.033). CONCLUSIONS: Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases.