Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial.

BACKGROUND: Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA). METHODS: Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients. RESULTS: Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L. CONCLUSIONS: Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection "lung". Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.

Case volume and specialization in critically ill emergency patients: a nationwide cohort study in Japanese ICUs.

BACKGROUND: Previous studies have explored the association between the number of cases and patient outcomes for critical illnesses such as sepsis and trauma, as well as various surgeries, with the expectation that a higher number of cases would have a more favorable effect on patient outcomes. The aim of this study was to elucidate the association among intensive care unit (ICU) case volume, specialization, and patient outcomes in critically ill emergency patients and to determine how ICU case volumes and specializations impact the outcomes of these patients in Japanese ICUs. METHODS: Utilizing data from the Japanese Intensive Care PAtient Database (JIPAD) from April 2015 to March 2021, this retrospective cohort study was conducted in 80 ICUs across Japan and included 72,214 emergency patients aged ≥ 16 years. The primary outcome measure was in-hospital mortality, and the secondary outcomes encompassed ICU mortality, 28-day mortality, ventilator-free days, and the lengths of ICU and hospital stays. Bayesian hierarchical generalized linear mixed models were used to adjust for patient- and ICU-level variables. RESULTS: This study revealed a significant association between a higher ICU case volume and decreased in-hospital mortality. In particular, ICUs with a higher percentage (> 75%) of emergency patients showed more pronounced effects, with the odds ratios for in-hospital mortality in the higher case volume quartiles (Q2, Q3, and Q4) being 0.92 (95% credible interval [CI]: 0.88-0.96), 0.70 (95% CI: 0.67-0.73), and 0.78 (95% CI: 0.73-0.83), respectively, compared with the lowest quartile (Q1). Similar trends were observed for various secondary outcomes. CONCLUSIONS: Higher ICU case volumes were significantly associated with lower in-hospital mortality rates in Japanese ICUs predominantly treating critically ill emergency patients. These findings emphasize the importance of ICU specialization and highlight the potential benefits of centralized care for critically ill emergency patients. These findings are potential insights for improving health care policy in Japan and may be valuable in emergency care settings in other countries with similar healthcare systems, after careful consideration of contextual differences.

Relationship of Endotracheal Tube Cuff Pressures with Changes in Body Positions of Critically Ill Patients on Mechanical Ventilation: An Observational Study.

Aims and background: Endotracheal tube cuff pressure (ETCP) is an important factor to determine the development of complications associated with invasive mechanical ventilation. To avoid preventable complications arising out of immobilization, frequent changes in body positioning are necessary. Such variations in body position can affect ETCP in critically ill patients who are on mechanical ventilation. So, our study aimed to assess the effect of changes in body position on ETCP in patients who are on mechanical ventilation. Materials and methods: This prospective observational study included 31 critically ill intubated patients. Each study subject was first placed in a neutral starting position with a 30º head elevation. Then, they were subjected to a sequential change in body position based on the 16 most used positions as part of the critical care unit's (CCUs) daily routine. Endotracheal tube cuff pressure was measured after each position change. Data were analyzed using standard statistical tests. Results: Statistically significant difference in ETCP was observed during anteflexion of neck, hyperextension of neck, left lateral flexion of neck, right lateral flexion of neck, left lateral rotation of neck, right lateral rotation of neck, 10o recumbent position, supine position, Trendelenburg position, and right lateral 30° and 45° positions. Maximum increase in ETCP was seen during anteflexion of neck (31 ± 4.5; 22-42 cm H2O). Conclusion: Our study demonstrates significant deviations in ETCP from the recommended range following changes in the body position of mechanically ventilated patients, highlighting the need for the measurement of ETCP after each position change and maintenance of the same within the target range. How to cite this article: Roy O, Dasgupta S, Chandra A, Biswas P, Choudhury A, Ghosh S, et al. Relationship of Endotracheal Tube Cuff Pressures with Changes in Body Positions of Critically Ill Patients on Mechanical Ventilation: An Observational Study. Indian J Crit Care Med 2024;28(1):36-40.

Myeloid-Derived Suppressor-like Cells as a Prognostic Marker in Critically Ill Patients: Insights from Experimental Endotoxemia and Intensive Care Patients.

Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15int M-MDSCs) was associated with overall mortality (p = 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15int M-MDSCs was a good predictor of mortality (p = 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4-1.0) and 0.86 (0.62-1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy.

Lung ultrasound and supine chest X-ray use in modern adult intensive care: mapping 30 years of advancement (1993-2023).

In critically ill patients with acute respiratory failure, thoracic images are essential for evaluating the nature, extent and progression of the disease, and for clinical management decisions. For this purpose, computed tomography (CT) is the gold standard. However, transporting patients to the radiology suite and exposure to ionized radiation limit its use. Furthermore, a CT scan is a static diagnostic exam for the thorax, not allowing, for example, appreciation of "lung sliding". Its use is also unsuitable when it is necessary to adapt or decide to modify mechanical ventilation parameters at the bedside in real-time. Therefore, chest X-ray and lung ultrasound are today's contenders for shared second place on the podium to acquire a thoracic image, with their specific strengths and limitations. Finally, electrical impedance tomography (EIT) could soon have a role, however, its assessment is outside the scope of this review. Thus, we aim to carry out the following points: (1) analyze the advancement in knowledge of lung ultrasound use and the related main protocols adopted in intensive care units (ICUs) over the latest 30 years, reporting the principal publications along the way, (2) discuss how and when lung ultrasound should be used in a modern ICU and (3) illustrate the possible future development of LUS.

Bioimpedance-assessed muscle wasting and its relation to nutritional intake during the first week of ICU: a pre-planned secondary analysis of Nutriti Study.

BACKGROUND: Muscle mass evaluation in ICU is crucial since its loss is related with long term complications, including physical impairment. However, quantifying muscle wasting with available bedside tools (ultrasound and bioimpedance analysis) must be more primarily understood. Bioimpedance analysis (BIA) provides estimates of muscle mass and phase angle (PA). The primary aim of this study was to evaluate muscle mass changes with bioimpedance analysis during the first 7 days after ICU admission. Secondary aims searched for correlations between muscular loss and caloric and protein debt. METHODS: Patients with an expected ICU-stay ≥ 72 h and the need for artificial nutritional support were evaluated for study inclusion. BIA evaluation of muscle mass and phase angle were performed at ICU admission and after 7 days. Considering the difference between ideal caloric and protein targets, with adequate nutritional macronutrients delivered, we calculated the caloric and protein debt. We analyzed the potential correlation between caloric and protein debt and changes in muscle mass and phase angle. RESULTS: 72 patients from September 1st to October 30th, 2019 and from August 1st to October 30th, 2021 were included in the final statistical analysis. Median age was 68 [59-77] years, mainly men (72%) admitted due to respiratory failure (25%), and requiring invasive mechanical ventilation for 7 [4-10] days. Median ICU stay was 8 [6-12] days. Bioimpedance data at ICU admission and after 7 days showed that MM and PA resulted significantly reduced after 7 days of critically illness, 34.3 kg vs 30.6 kg (p < 0.0001) and 4.90° vs 4.35° (p = 0.0004) respectively. Mean muscle loss was 3.84 ± 6.7 kg, accounting for 8.4% [1-14] MM reduction. Correlation between caloric debt (r = 0.14, p = 0.13) and protein debt (r = 0.18, p = 0.13) with change in MM was absent. Similarly, no correlation was found between caloric debt (r = -0.057, p = 0.631) and protein debt (r = -0.095, p = 0.424) with changes in PA. CONCLUSIONS: bioimpedance analysis demonstrated that muscle mass and phase angle were significantly lower after 7 days in ICU. The total amount of calories and proteins does not correlate with changes in muscle mass and phase angle.

Relationship between ultrasound measurement of quadriceps muscle and nutritional status in ICU patients in a high-complexity trauma care hospital

Introduction Muscle mass assessment of critically ill patients is essential to be part of the nutritional diagnosis in hospital care. Thus, the evaluation of more specific techniques for that purpose is needed. The present study aimed to investigate the association of quadriceps muscle thickness (QMT), measured by ultrasound (US), with the nutritional status of critically ill patients in a referral high-complexity trauma care hospital. Methods A cross-sectional observational study was conducted in the intensive care units (ICUs) in a tertiary hospital in Brazil. The sample comprised 30 critically ill trauma patients admitted between February and March 2022. The methodology involved evaluating muscle mass and comparing nutritional status through mid-upper arm circumference measurements and US assessments. Specifically, the QMT was quantified using US at a predefined site between the iliac crest and the proximal border of the patella. Results The Kruskal-Wallis test indicated variability in QMT between the nutritional status groups, with statistical significance reached after excluding the overweight group (H(2) = 7.532, p = 0.023). The moderate malnutrition group exhibited notably lower QMT. Sensitivity analyses using bootstrap and Monte Carlo methods showed moderate trends toward significance. A positive correlation was found between QMT and mid-upper arm circumference adequacy (p < 0.05), demonstrating fair to moderate correlation (rs = 0.531). Conclusion Significant changes in QMT were detected by ultrasound assessment in moderate malnutrition patients compared to patients of other nutritional statuses. Ultrasound may be a valuable technique for monitoring muscle integrity in critically ill patients.

To Crush or Not to Crush: Administering Dabrafenib and Trametinib Through a Nasogastric Tube in a Critically Ill Patient With Nonsmall Cell Lung Cancer - A Case Report and Review of Literature of Targeted Therapies Given Through Enteral Feeding Tubes.

Up to 71% of lung cancer patients admitted to the ICU are newly diagnosed. The decision to initiate cancer directed treatments in lung cancer patients admitted to the ICU remains complex. For those with identified oncogene driver mutations, targeted therapies with rapid and high response rates are attractive treatment options. However, mechanically ventilated patients face additional barriers in which enteral tube administration of oral therapies may require tablets or capsules to be crushed or opened and diluted. Data on the pharmacodynamics and pharmacokinetics of this alternative route of administration are often very limited. Here we describe the first case report of an intubated patient with newly diagnosed NSCLC who was successfully treated with opened dabrafenib capsules and crushed trametinib tablets administered through a nasogastric tube. We also provide a review of the existing literature on feeding tube administration of commonly used tyrosine kinase inhibitors in lung cancer. Tyrosine kinase inhibitors administered through feeding tubes can lead to a clinically meaningful recovery in critically ill patients.

Specific Training Improves the Detection and Management of Patient-Ventilator Asynchrony.

BACKGROUND: Patient-ventilator asynchrony is common in patients undergoing mechanical ventilation. The proportion of health-care professionals capable of identifying and effectively managing different types of patient-ventilator asynchronies is limited. A few studies have developed specific training programs, but they mainly focused on improving patient-ventilator asynchrony detection without assessing the ability of health-care professionals to determine the possible causes. METHODS: We conducted a 36-h training program focused on patient-ventilator asynchrony detection and management for health-care professionals from 20 hospitals in Latin America and Spain. The training program included 6 h of a live online lesson during which 120 patient-ventilator asynchrony cases were presented. After the 6-h training lesson, health-care professionals were required to complete a 1-h training session per day for the subsequent 30 d. A 30-question assessment tool was developed and used to assess health-care professionals before training, immediately after the 6-h training lecture, and after the 30 d of training (1-month follow-up). RESULTS: One hundred sixteen health-care professionals participated in the study. The median (interquartile range) of the total number of correct answers in the pre-training, post-training, and 1-month follow-up were significantly different (12 [8.75-15], 18 [13.75-22], and 18.5 [14-23], respectively). The percentages of correct answers also differed significantly between the time assessments. Study participants significantly improved their performance between pre-training and post-training (P < .001). This performance was maintained after a 1-month follow-up (P = .95) for the questions related to the detection, determination of cause, and management of patient-ventilator asynchrony. CONCLUSIONS: A specific 36-h training program significantly improved the ability of health-care professionals to detect patient-ventilator asynchrony, determine the possible causes of patient-ventilator asynchrony, and properly manage different types of patient-ventilator asynchrony.

Combination of serum and peritoneal 1.3-beta-D-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study.

BACKGROUND: Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC. METHODS: This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements. RESULTS: Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%. CONCLUSION: In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Association between diastolic dysfunction and fluid balance in critically ill patients during weaning from mechanical ventilation / Asociación entre la disfunción diastólica y el balance de hídrico en pacientes críticos durante el destete de la ventilación mecánica

Objective: To assess the role of diastolic dysfunction and fluid balance in weaning failure. Design: Prospective, observational, single center. Setting: Intensive care unit of a university hospital. Patients: Adult patients on mechanical ventilation for more than 48 h who underwent a spontaneous breathing trial (SBT). Interventions: Echocardiography was performed immediately before and at the end of SBT. Patients were classified into two groups according to weaning outcome. Main variable of interest: Weaning failure. Results: Among 89 patients included, weaning failure occurred in 33 patients (37%). Isolated diastolic dysfunction at the end of the SBT was more frequent in the failure group (39.3% vs. 17.8%, p = 0.025). Average daily fluid balance from ICU admission until first SBT was less negative in patients who failed than in those who succeed in the weaning (−648 mL [−884 to -138] vs. −893 mL [−1284 to −501], p = 0.007). Average daily fluid balance from the first SBT until the ICU discharge was more negative in the weaning failure than in the success group (−973 mL [−1493 to −201] vs. −425 mL [−1065 to 12], p = 0.034). Cox regression analysis showed that diastolic dysfunction was not an independent factor related to weaning failure but needed the association of positive fluid balance and age. Conclusions: Weaning failure due to diastolic dysfunction is highly related to fluid balance, and the deleterious effect of fluid balance on diastolic function is associated with age The timing of fluid removal could play a key role in this scenario. (AU)

Objetivo: Evaluar el papel de la disfunción diastólica (DD) y el balance hídrico en el fracaso del destete de la ventilación mecánica. Diseño: Prospectivo, observacional.Ámbito: Unidad de cuidados intensivos hospital universitario. Pacientes: Pacientes adultos con ventilación mecánica más de 48 h sometidos a una prueba de respiración espontánea (SBT).Intervenciones: Ecocardiografía antes y al final del SBT. Los pacientes se clasificaron en dos grupos según el resultado del destete. Variable de interés principal: Fracaso del destete. Resultados: Se incluyeron 89 pacientes, el fracaso del destete ocurrió en 33 (37%). La DD al final de la SBT fue más frecuente en el grupo de fracaso (39,3% vs 17,8%, p = 0,025). El balance hídrico diario desde el ingreso en UCI hasta la SBT fue menos negativo en los pacientes que fracasaron que en los que tuvieron éxito del destete (−648 mL [-884 a -138] vs −893 mL [-1284 a -501], p = 0,007). El balance hídrico diario desde el primer SBT hasta el alta de UCI fue más negativo en el grupo de fracaso que en el de éxito (−973 ml [−1493 a −201] vs. −425 ml [−1065 a 12], p = 0,034). La regresión de Cox mostró que la DD no era un factor independiente relacionado con el fracaso, necesitando la asociación del balance hídrico y la edad. Conclusiones: El fracaso del destete debido a DD se relaciona con el balance hídrico, incrementando su efecto nocivo con la edad. El momento de inicio del balance hídrico negativo puede jugar un papel clave en el fracaso. (AU)

Characterization of Pulmonary Bacteriobiota in Critically Ill Patients in Southern Peru through Next-Generation Sequencing Technology.

Sequence variation in the 16S gene is widely used to characterize diverse microbial communities. This was the first pilot study carried out in our region where the pulmonary microbiota of critically ill patients was investigated and analyzed, with the aim of finding a specific profile for these patients that can be used as a diagnostic marker. An study of critical patients mechanically ventilated for non-respiratory indications, in a polyvalent intensive care unit, was carried out; samplee were extracted by endotracheal aspiration and subsequently the microbiota was characterized through Next-Generation Sequencing Technology (NGS). The predominant phyla among the critically ill patients were Proteobacteria, Firmicutes and Bacteroidata. In the surviving patients group, the predominant phyla were Proteobacteria, Bacteroidata and Firmicutes, in the group of deceased patients thy were Firmicutes, Proteobacteria, and Bacteroidata. We found a decrease in commensal bacteria in deceased patients and a progressive increase in in-hospital germs.

Acute kidney injury associated with piperacillin-tazobactam versus other antibiotics combined with vancomycin in critically ill patients: A retrospective cohort study.

Introduction: Evidence of acute kidney injury (AKI) induced by piperacillin-tazobactam (Piptazo) versus other broad-spectrum antibiotics (BSA) combined with vancomycin has been established in the literature. However, there is limited evidence regarding these combinations among critically ill patients. This study assessed the risk of nephrotoxicity of Piptazo versus other BSA as an add-on to vancomycin among patients admitted to an intensive care unit (ICU). Methods: We have reviewed patients' charts retrospectively to investigate AKI incidence among ICU patients receiving Piptazo versus other BSA as an add-on to vancomycin. Furthermore, we have assessed the duration of AKI and ICU stay, as well as the association between patients' criteria and risk of AKI using logistic regression analyses. Results: A total of 79 patients were included, 50 patients received the Piptazo combination while 29 patients received other BSA combinations. Almost 52 % of the patients in the Piptazo group developed AKI while only 37.9 % of those in the BSA group did, yet the difference was not statistically significant (p = 0.22). On the other hand, the risk of AKI was highly associated with vancomycin trough concentration above 20 mcg/mL, nephrotoxic medications, and African descent (OR 7.1, 95 %CI 1.96-25.84, OR 3.94, 95 %CI 1.27-12.2, OR 3.53, 95 %CI 1.1-11.27, respectively). Conclusion: Although the difference in AKI risk was not statistically significant between Piptazo versus BSA groups, the elevated trough concentration of vancomycin and the concomitant use of nephrotoxic medications, were found to increase the risk of AKI, independently of the combined antibiotics used.

Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 (J-ReCIP 2023).

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.

The role of beta-blocker drugs in critically ill patients: a SIAARTI expert consensus statement.

BACKGROUND: The role of ß-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of ß-blockers in critically ill patients are still lacking. The purpose of this document is to support the clinical decision-making process regarding the use of ß-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient's care process. METHODS: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of ß-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus. RESULTS: The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of ß-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration. CONCLUSION: ß-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first.

Prophylactic platelet transfusion response in critically ill patients: a prospective multicentre observational study.

BACKGROUND: Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes. METHODS: This prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18-24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensitivity analyses were conducted in patients with and without haematology malignancy and chemotherapy. RESULTS: Poor platelet transfusion response occurred in 349 of the 472 (73.9%) prophylactic platelet transfusions and in 141/181 (77.9%) patients. The mixed-effect model identified haemoglobin at ICU admission (odds ratio (OR): 0.79 [95% confidence interval (CI) 0.7-0.89]) and body mass index (BMI) (OR: 0.93 [0.89-0.98]) being positively and independently associated with platelet transfusion response, while a haematological malignancy (OR 1.93 [1.09-3.43]), sepsis as primary ICU admission diagnosis (OR: 2.81 [1.57-5.03]), SOFA score (OR 1.10 [1.03; 1.17]) and maximum storage duration of platelet (OR: 1.24 [1.02-1.52]) were independently associated with a suboptimal platelet increment. Clinical outcomes did not differ between groups, nor the requirement for red blood cells. Poor platelet transfusion response was found in 93.5% of patients with haematology malignancy and chemotherapy. CONCLUSIONS: In this study of critically ill patients, of whom more than half had bone marrow failure, almost three quarters of prophylactic platelet transfusions led to suboptimal platelet increment measured 18 to 24 h following platelet transfusion. Platelet storage duration was the only factor associated with poor platelet response that may be accessible to intervention. Trial registration in October 2017: ClinicalTrials.gov: NCT03325140.

The Significance of Bayesian Pharmacokinetics in Dosing for Critically Ill Patients: A Primer for Clinicians Using Vancomycin as an Example.

Antibiotic use is becoming increasingly challenging with the emergence of multidrug-resistant organisms. Pharmacokinetic (PK) alterations result from complex pathophysiologic changes in some patient populations, particularly those with critical illness. Therefore, antibiotic dose individualization in such populations is warranted. Recently, there have been advances in dose optimization strategies to improve the utilization of existing antibiotics. Bayesian-based dosing is one of the novel approaches that could help clinicians achieve target concentrations in a greater percentage of their patients earlier during therapy. This review summarizes the advantages and disadvantages of current approaches to antibiotic dosing, with a focus on critically ill patients, and discusses the use of Bayesian methods to optimize vancomycin dosing. The Bayesian method of antibiotic dosing was developed to provide more precise predictions of drug concentrations and target achievement early in therapy. It has benefits such as the incorporation of personalized PK/PD parameters, improved predictive abilities, and improved patient outcomes. Recent vancomycin dosing guidelines emphasize the importance of using the Bayesian method. The Bayesian method is able to achieve appropriate antibiotic dosing prior to the patient reaching the steady state, allowing the patient to receive the right drug at the right dose earlier in therapy.

Reappraisal of intra-abdominal candidiasis: insights from peritoneal fluid analysis.

BACKGROUND: The understanding of high mortality associated with intra-abdominal candidiasis (IAC) remains limited. While Candida is considered a harmless colonizer in the digestive tract, its role as a true pathogen in IAC is still debated. Evidence regarding Candida virulence in the human peritoneal fluid are lacking. We hypothesized that during IAC, Candida albicans develops virulence factors to survive to new environmental conditions. The objective of this observational exploratory monocentric study is to investigate the influence of peritoneal fluid (PF) on the expression of C. albicans virulence using a multimodal approach. MATERIALS AND METHODS: A standardized inoculum of a C. albicans (3.106 UFC/mL) reference strain (SC5314) was introduced in vitro into various PF samples obtained from critically ill patients with intra-abdominal infection. Ascitic fluids (AFs) and Sabouraud medium (SBD) were used as control groups. Optical microscopy and conventional culture techniques were employed to assess the morphological changes and growth of C. albicans. Reverse transcriptase qPCR was utilized to quantify the expression levels of five virulence genes. The metabolic production of C. albicans was measured using the calScreener™ technology. RESULTS: A total of 26 PF samples from patients with secondary peritonitis were included in the study. Critically ill patients were mostly male (73%) with a median age of 58 years admitted for urgent surgery (78%). Peritonitis was mostly hospital-acquired (81%), including 13 post-operative peritonitis (50%). The infected PF samples predominantly exhibited polymicrobial composition. The findings revealed substantial variability in C. albicans growth and morphological changes in the PF compared to ascitic fluid. Virulence gene expression and metabolic production were dependent on the specific PF sample and the presence of bacterial coinfection. CONCLUSIONS: This study provides evidence of C. albicans virulence expression in the peritoneal fluid. The observed variability in virulence expression suggests that it is influenced by the composition of PF and the presence of bacterial coinfection. These findings contribute to a better understanding of the complex dynamics of intra-abdominal candidiasis and advocate for personalized approach for IAC patients. Trial registration https://clinicaltrials.gov/ (NCT05264571; February 22, 2022).