An LCMS/MS method for the simultaneous determination of ten antimicrobials and its application in critically ill patients.

Significant pharmacokinetic variation occurs in critically ill patients, leading to underexposure to antibiotics and poor prognosis. In this study, we developed a simple, sensitive, and fast liquid chromatography tandem mass spectrometry (LCMS/MS) platform for the simultaneous quantification of 8 antibacterial and 2 antifungal drugs, which is optimally suited for clinically efficient, real-time therapeutic drug monitoring (TDM). Multiple reaction monitoring (MRM) mass spectrometry was used in this method, and samples were prepared via protein precipitation with methanol. Chromatographic separation was accomplished on a BGIU Column-U02 (2.1ｘ50 mm, 3 µm), with six stable isotopes and one analog as an internal standard. The overall turnaround time of the assay was 5 minutes. All the drugs tested (piperacillin, cefoperazone, meropenem, levofloxacin, moxifloxacin, daptomycin, linezolid, vancomycin, fluconazole and voriconazole) were linear in the test concentration range (r ≥ 0.9900), the accuracy was 95 %-111 %, the precision variation coefficient was greater than or equal to 10 %, the lower limit of quantitation was 0.31-7.51 mg/L, and the coefficient of variation of the matrix factor was less than 10 %. The recovery rates ranged from 85 % to 115 %, and the antibiotics were stable at 4°C and -20°C for 6 days, with an offset of greater than or equal to 15 %. This method was successfully applied to routine TDM in 252 elderly critically ill patients.

Aromatherapy for Sleep Promotion in the ICU: Insights and Future Directions.

BACKGROUND: The effects of inhaled aromatherapy on sleep quality in critically ill patients in the intensive care unit (ICU) have been widely studied. Specific essential oil combinations have been highlighted for their potential to promote sleep in these patients. AIM: To offer additional insights and future directions for the application of aromatherapy in improving sleep quality among critically ill patients, considering the current evidence and addressing gaps in research. DISCUSSION: While certain blends of essential oils, such as lavender, Matricaria recutita, and neroli, have shown promise, other studies have produced mixed results regarding the optimal aromatherapy interventions. Integrating aromatherapy with other non-pharmacological approaches, such as earplugs, eye masks, or music, may offer enhanced sleep benefits. Further research is needed to evaluate aromatherapy's effects on specific populations, such as intubated patients, and to assess feasibility, cost-effectiveness, and potential adverse effects. CONCLUSION: Aromatherapy shows promise for improving sleep quality in critically ill patients but should be integrated with other evidence-based, non-pharmacological interventions. Addressing research gaps is crucial for developing comprehensive strategies to enhance sleep quality in ICU settings.

Left Ventricular Diastolic Dysfunction in the Critically Ill: The Rubik's Cube of Echocardiography.

How to cite this article: Kumar V. Left Ventricular Diastolic Dysfunction in the Critically Ill: The Rubik's Cube of Echocardiography. Indian J Crit Care Med 2024;28(9):813-815.

Acute kidney injury developed in the intensive care unit: a population-based prospective cohort study in the Brazilian Amazon.

The Brazilian Amazon is a vast area with limited health care resources. To assess the epidemiology of critically ill acute kidney injury (AKI) patients in this area, a prospective cohort study of 1029 adult patients of the three intensive care units (ICUs) of Rio Branco city, the capital of Acre state, were evaluated from February 2014 to February 2016. The incidence of AKI was 53.3%. Risk factors for AKI included higher age, nonsurgical patients, admission to the ICU from the ward, higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores at ICU admission, and positive fluid balance > 1500 ml/24 hours in the days before AKI development in the ICU, with aOR of 1.3 (95% CI 1.03-1.23), 1.47 (95% CI 1.07-2.03), 1.96 (95% CI 1.40-2.74), 1.05 (95% CI 1.03-1.08) for each unit increase, and 1.62 (95% CI 1.16-2.26), respectively. AKI was associated with higher ICU mortality (aOR 2.03, 95% CI 1.29-3.18). AKI mortality was independently associated with higher age, nonsurgical patients, sepsis at ICU admission, presence of shock or use of vasoactive drugs, mechanical ventilation and mean positive fluid balance in the ICU > 1500 ml/24 hours, both during ICU follow-up, with aOR 1.27 (95% CI 1.14-1.43) for each 10-year increase, 1.64 (95% CI 1.07-2.52), 2.35 (95% CI 1.14-4.83), 1.88 (95% CI 1.03-3.44), 6.73 (95% CI 4.08-11.09), 2.31 (95% CI 1.52-3.53), respectively. Adjusted hazard ratios for AKI mortality 30 and 31-180 days after ICU discharge were 3.13 (95% CI 1.84-5.31) and 1.69 (95% CI 0.99-2.90), respectively. AKI incidence was strikingly high among critically ill patients in the Brazilian Amazon. The AKI etiology, risk factors and outcomes were similar to those described in high-income countries, but mortality rates were higher.

Advanced lung cancer inflammation index is associated with mortality in critically ill patients with heart failure.

AIMS: Nutrition and inflammation status play a vital role in the prognosis of patients with heart failure (HF). This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a novel composite indicator of inflammation and nutrition, and short-term mortality among critically ill patients with HF. METHODS: This retrospective study included 548 critically ill patients with HF from the MIMIC-IV database. ALI was computed using body mass index, serum albumin and neutrophil-lymphocyte ratio. The primary endpoint was all-cause in-hospital mortality, and the secondary endpoint was 90 day mortality. Kaplan-Meier survival curve analysis with long-rank test and Cox proportional hazards regression models were employed to assess the relationship between baseline ALI and short-term mortality risk. The incremental predictive ability of ALI was evaluated by C-statistic, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The average age of 548 patients was 72.2 (61.9, 82.1) years, with 60% being male. Sixty-three patients (11.5%) died in the hospital, and 114 patients (20.8%) died within 90 days of intensive care unit admission. The Kaplan-Meier analysis revealed that the cumulative incidences of both in-hospital and 90 day mortality were significantly higher in patients with lower ALI (log-rank test, in-hospital mortality: P < 0.001; 90 day mortality: P < 0.001). The adjusted Cox proportional hazard model revealed that ALI was inversely associated with both in-hospital and 90 day mortality after adjusting for confounders [hazard ratio (HR) (95% confidence interval) (CI): 0.97 (0.94, 0.99), P = 0.035; HR (95% CI): 0.62 (0.39, 0.99), P = 0.046]. A linear relationship was observed between ALI and in-hospital mortality (P for non-linearity = 0.211). The addition of ALI significantly improved the prognostic ability of GWTG-HF score in the in-hospital mortality [C-statistic improved from 0.62 to 0.68, P = 0.001; continuous NRI (95% CI): 0.44 (0.20, 0.67), P < 0.001; IDI (95% CI): 0.03 (0.01, 0.04), P < 0.001] and 90 day mortality [C-statistic improved from 0.63 to 0.70, P < 0.001; continuous NRI (95% CI): 0.31 (0.11, 0.50), P = 0.002; IDI (95% CI): 0.01 (0.00, 0.02), P = 0.034]. Subgroup analysis revealed stronger correlations between ALI and in-hospital mortality in males and patients aged over 65 years (interaction P = 0.031 and 0.010, respectively). The C-statistic of in-hospital mortality in patients over 65 years was 0.66 (95% CI: 0.58, 0.74). CONCLUSIONS: ALI at baseline can independently predict the risk of short-term mortality in critically ill patients with HF, with lower ALI significantly associated with higher mortality. Further large prospective research with extended follow-up periods is necessary to validate the findings of this study.

Creatinine clearance/eGFR ratio: a simple index for muscle mass related to mortality in ICU patients.

INTRODUCTION: In patients admitted to the intensive care unit (ICU), muscle mass is inversely associated with mortality. Although muscle mass can be estimated with 24-h urinary creatinine excretion (UCE), its use for risk prediction in individual patients is limited because age-, sex-, weight- and length-specific reference values for UCE are lacking. The ratio between measured creatinine clearance (mCC) and estimated glomerular filtration rate (eGFR) might circumvent this constraint. The main goal was to assess the association of the mCC/eGFR ratio in ICU patients with all-cause hospital and long-term mortality. METHODS: The mCC/eGFR ratio was determined in patients admitted to our ICU between 2005 and 2021 with KDIGO acute kidney injury (AKI) stage 0-2 and an ICU stay ≥ 24 h. mCC was calculated from UCE and plasma creatinine and indexed to 1.73 m2. mCC/eGFR was analyzed by categorizing patients in mCC/eGFR quartiles and as continuous variable. RESULTS: Seven thousand five hundred nine patients (mean age 61 ± 15 years; 38% female) were included. In-hospital mortality was 27% in the lowest mCC/eGFR quartile compared to 11% in the highest quartile (P < 0.001). Five-year post-hospital discharge actuarial mortality was 37% in the lowest mCC/eGFR quartile compared to 19% in the highest quartile (P < 0.001). mCC/eGFR ratio as continuous variable was independently associated with in-hospital mortality in multivariable logistic regression (odds ratio: 0.578 (95% CI: 0.465-0.719); P < 0.001). mCC/eGFR ratio as continuous variable was also significantly associated with 5-year post-hospital discharge mortality in Cox regression (hazard ratio: 0.27 (95% CI: 0.22-0.32); P < 0.001). CONCLUSIONS: The mCC/eGFR ratio is associated with both in-hospital and long-term mortality and may be an easily available index of muscle mass in ICU patients.

Secondary Sclerosing Cholangitis (SSC): An Underrecognized Complication of Severe COVID-19 Pneumonitis.

COVID-19-secondary sclerosing cholangitis (COVID-SSC) is a distinct subset of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) that presents after COVID-19 infection with alkaline phosphatase predominant elevation of liver enzymes. COVID-SSC typically presents within three months of COVID-19 diagnosis and most commonly occurs following severe COVID-19 infection. COVID-SSC can have different clinical degrees of severity, ranging from clinically latent, as shown in this case report, to severely symptomatic, requiring a liver transplant or leading to patient death.  We present a case of COVID-SSC that presented in an asymptomatic patient months after severe COVID pneumonitis requiring prolonged intubation who was initially misdiagnosed with autoimmune hepatitis and found to have early cirrhosis at the time of diagnosis. The case presented was initially clinically silent and overlooked for months. In the aftermath of severe COVID-19 infection, COVID-SSC should be included in the differential diagnosis of unclear cholestasis, and general practitioners should have a high index of suspicion when encountering disproportionate elevation of alkaline phosphatase in patients with a history of COVID-19, in particular, those requiring intensive care unit (ICU) level cares.

Impact of nutrition-related laboratory tests on mortality of patients who are critically ill using artificial intelligence: A focus on trace elements, vitamins, and cholesterol.

BACKGROUND: This study aimed to understand the collective impact of trace elements, vitamins, cholesterol, and prealbumin on patient outcomes in the intensive care unit (ICU) using an advanced artificial intelligence (AI) model for mortality prediction. METHODS: Data from ICU patients (December 2016 to December 2021), including serum levels of trace elements, vitamins, cholesterol, and prealbumin, were retrospectively analyzed using AI models. Models employed included category boosting (CatBoost), extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), and multilayer perceptron (MLP). Performance was evaluated using area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, and F1-score. The performance was evaluated using 10-fold crossvalidation. The SHapley Additive exPlanations (SHAP) method provided interpretability. RESULTS: CatBoost emerged as the top-performing individual AI model with an AUROC of 0.756, closely followed by LGBM, MLP, and XGBoost. Furthermore, the ensemble model combining these four models achieved the highest AUROC of 0.776 and more balanced metrics, outperforming all models. SHAP analysis indicated significant influences of prealbumin, Acute Physiology and Chronic Health Evaluation II score, and age on predictions. Notably, the ratios of selenium to age and low-density lipoprotein to total cholesterol also had a notable impact on the models' output. CONCLUSION: The study underscores the critical role of nutrition-related parameters in ICU patient outcomes. Advanced AI models, particularly in an ensemble approach, demonstrated improved predictive accuracy. SHAP analysis offered insights into specific factors influencing patient survival, highlighting the need for broader consideration of these biomarkers in critical care management.

Association between lactate/albumin ratio and 28-day all-cause mortality in critically ill patients with acute myocardial infarction.

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Early identification of high-risk patients is crucial for timely interventions and improved outcomes. The lactate/albumin ratio (LAR) has been suggest as a significant correlate for assessing the risk of mortality in critically ill patients. This study aimed to utilize the American eICU Collaborative Research Database to explore the association between baseline LAR and all-cause mortality within 28 days in ICU of critically ill patients diagnosed with AMI. We conducted a retrospective cohort study of 989 AMI patients from the eICU Collaborative Research Database. Patients were included based on ICD-9 code 410 and the universal definition of AMI. LAR was calculated as the ratio of baseline lactate to albumin levels within the first 24 h of ICU admission. The outcome was all-cause mortality within 28 days after ICU admission. Multivariable logistic regression models were used to evaluate the independent association between LAR and the risk of death, adjusting for potential confounders including demographics, comorbidities, vital signs, and laboratory parameters. Subgroup analyses and nonlinear modeling were performed to further explore the relationship. Of the 989 AMI patients, 171 (17.3%) died within 28 days after ICU admission. Patients who died had significantly higher LAR compared to survivors (1.66 vs. 0.96, p < 0.001). Multivariable analysis showed that each unit increase in LAR was associated with a 2.15-fold higher risk of all-cause mortality within 28 days after ICU admission (95% CI: 1.64-2.83, p < 0.001). Subgroup analyses confirmed the consistent association across different patient characteristics. Nonlinear modeling revealed a threshold effect, where LAR above 2.15 was no longer significantly associated with mortality. Kaplan-Meier survival analysis demonstrated lower survival probabilities for patients with higher LAR(1.0526-5.8235). The findings suggest that a higher LAR was associated with an increased risk of 28-day all-cause mortality for critically ill patients with AMI after ICU admission.

Association between serum anion gap and 28-day mortality in critically ill patients with infective endocarditis: a retrospective cohort study from MIMIC IV database.

BACKGROUND: The relationship between serum anion gap (AG) and 28-day mortality in critically ill patients with infective endocarditis is currently not well established. OBJECTIVE: This study aims to investigate the impact of serum AG on 28-day mortality in critically ill patients with infective endocarditis. METHODS: A retrospective cohort study was conducted involving 449 participants diagnosed with infective endocarditis and admitted to intensive care units (ICU). Vital signs, laboratory parameters and comorbidity were collected for all participants to analyze the association between anion gap levels and 28-day mortality. RESULTS: A total of 449 critically ill patients with infective endocarditis (IE) were included in the study. The mean age was 57 years, and 64% were male. The overall 28-day mortality rate was 20%. A greater AG on admission were significantly associated with increased 28-day mortality in unadjusted analysis (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.09-1.18; p < 0.001). After adjusting for all confounders, the association remained significant (adjusted HR 1.07; 95% CI 1.02-1.13; p = 0.003). When AG was converted into categorial variables (quartiles), the risk of 28-day mortality in the greatest Q4 group was significantly higher compared with that in the lowest Q1 group (model 4: HR = 2.62, 95%CI: 1.17-5.83, p = 0.019). Subgroup analysis showed consistent results across different groups. CONCLUSION: A greater AG on admission were independently associated with increased 28-day mortality in critically ill patients with IE. These findings suggest that the AG can serve as a prognostic marker in this population, aiding in risk stratification and guiding clinical management.

Changes of Procalcitonin Kinetics According to Renal Clearance in Critically Ill Patients with Primary Gram-Negative Bloodstream Infections.

Objective: This study aimed to investigate the relationship between procalcitonin (PCT) kinetic and estimated glomerular filtration rates (eGFR) in critically ill patients who had Gram-negative primary bloodstream infection (GN-BSI) and responded to the antimicrobial therapy. Materials and Methods: This single-centered study was retrospective and observational. Critically ill GN-BSI patients over 18 years old who had clinical and microbiological responses to antibiotic treatment were included in the study. Patients were divided into two groups according to eGFR (eGFR <30 mL/min/1.73m2 and ≥30 mL/min/1.73m2) and compared for PCT kinetic at seven different measurement points as initial, first, third, fifth, seventh, tenth, and fourteenth days. Results: The study included 138 patients. Initial PCT levels were higher in patients with eGFR <30 mL/min/1.73m2 (4.58 [1.36-39.4] ng/mL) than in eGFR ≥30 mL/min/1.73m2 (0.91 [0.32-10.2]) (p<0.001). This elevation was present at all measurement points (p<0.05). The decrease in PCT values by ≥30% (26.0% vs 47.9%; p=0.024) on the third day and ≥50% (69.2% vs 76.6%; p=0.411) on the fifth day was less in the low eGFR (<30 mL/min/1.73m2) group. The effect of low GFR on serum PCT kinetic was present in both fermenter and non-fermenter GN-BSIs but was more prominent in the fermenter group. Conclusion: Serum PCT levels during therapy were higher in patients with low eGFR. Early PCT (<5 days) response was not obtained in non-fermenter GN-BSI patients with low eGFR. Antibiotic revision decisions should be made more carefully in patients with low eGFR due to high initial PCT levels and slow PCT kinetic.

A Benign Finding of Hemorrhagic Pancreatitis.

Hemorrhagic pancreatitis is a rare cause of hypovolemic shock. It presents as silent bleeding, with signs of hypovolemic shock and abdominal pain eventually culminating in life-threatening bleeding. This case study delves into a case of hemorrhagic pancreatitis in a 49-year-old male. Notably, he has a history of recurrent lower extremity (LE) deep vein thrombosis (DVT) and atrial fibrillation (AF) on Coumadin. He came in with shortness of breath (SOB) and was admitted for acute hypoxic respiratory failure secondary to Influenza A. A few days into admission, the patient developed acute cardiogenic shock, septic shock, and acute respiratory distress syndrome (ARDS). The patient developed rectal bleeding with a decrease in hemoglobin and hematocrit. A computed tomography (CT) of the chest, abdomen, and pelvis (CAP) without (w/o) contrast was performed to find a source. It showed hemorrhagic pancreatitis in the head/tail region. The bleeding resolved on its own without interventions or blood transfusion. Hemorrhagic pancreatitis carries a high mortality rate. In this case, it had an insidious onset with self-resolution, a rare case. Physicians should make quick referrals for surgical resection in hopes of better outcomes.

Interpretable machine learning model for new-onset atrial fibrillation prediction in critically ill patients: a multi-center study.

BACKGROUND: New-onset atrial fibrillation (NOAF) is the most common arrhythmia in critically ill patients admitted to intensive care and is associated with poor prognosis and disease burden. Identifying high-risk individuals early is crucial. This study aims to create and validate a NOAF prediction model for critically ill patients using machine learning (ML). METHODS: The data came from two non-overlapping datasets from the Medical Information Mart for Intensive Care (MIMIC), with MIMIC-IV used for training and subset of MIMIC-III used as external validation. LASSO regression was used for feature selection. Eight ML algorithms were employed to construct the prediction model. Model performance was evaluated based on identification, calibration, and clinical application. The SHapley Additive exPlanations (SHAP) method was used for visualizing model characteristics and individual case predictions. RESULTS: Among 16,528 MIMIC-IV patients, 1520 (9.2%) developed AF post-ICU admission. A model with 23 variables was built, with XGBoost performing best, achieving an AUC of 0.891 (0.873-0.888) in validation and 0.769 (0.756-0.782) in external validation. Key predictors included age, mechanical ventilation, urine output, sepsis, blood urea nitrogen, percutaneous arterial oxygen saturation, continuous renal replacement therapy and weight. A risk probability greater than 0.6 was defined as high risk. A friendly user interface had been developed for clinician use. CONCLUSION: We developed a ML model to predict the risk of NOAF in critically ill patients without cardiac surgery and validated its potential as a clinically reliable tool. SHAP improves the interpretability of the model, enables clinicians to better understand the causes of NOAF, helps clinicians to prevent it in advance and improves patient outcomes.

Inconsistencies in the Indian Guidelines for the Prescription of Antibiotics for Critically Ill Patients.

The recently formulated guidelines by Khilnani GC et al. for the prescription of antibiotics for critically ill patients present an extensive compilation of evidence and recommendations. Despite their comprehensive nature, several inconsistencies need addressing. In this commentary, we delve into some of these discrepancies in the order in which they appeared in the guidelines, starting with the misrepresentation of "nonbronchoscopic bronchoalveolar lavage (BAL)" and "mini BAL" as different techniques when they are, in fact, identical. Secondly, the Centers for Disease Control and Prevention (CDC) in the year 2013 replaced the older, unreliable ventilator-associated pneumonia (VAP) definition with ventilator-associated events (VAE). This new VAE definition eliminates subjectivity in pneumonia diagnosis by focusing on objective criteria for ventilator support changes, avoiding dependence on potentially inaccurate chest X-rays and inconsistent medical record keeping. Thus, using the term VAP in the Indian guidelines seems regressive. Furthermore, the recommendation for routine anaerobic coverage in aspiration pneumonia is outdated and unsupported by current evidence. Lastly, while endorsing multiplex polymerase chain reaction (PCR) for pathogen identification, the guidelines fail to adequately address its limitations and the risk of overdiagnosis. How to cite this article: Raj N, Nath SS, Singh V, Agarwal J. Inconsistencies in the Indian Guidelines for the Prescription of Antibiotics for Critically Ill Patients. Indian J Crit Care Med 2024;28(10):908-911.

Identifying risk factors for acute respiratory distress syndrome in critically ill patients: a retrospective study.

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition that can develop in critically ill patients. Early identification of risk factors associated with ARDS development is essential for timely intervention and improved patient outcomes. This study aimed to investigate the potential predictors of ARDS in critically ill patients admitted to the intensive care unit (ICU). Methods: We conducted a retrospective study involving 502 critically ill patients admitted to the ICUs of three hospitals. Demographic and clinical data, including laboratory test results, were collected during their ICU stay. Multivariable logistic regression analysis was performed to identify independent risk factors associated with the development of ARDS. Results: Among the 502 critically ill patients, 104 (20.7%) patients developed ARDS during their ICU stay, with a median time to development of 5.2 days. Multivariable logistic regression analysis revealed that age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.13; P = 0.002), C-reactive protein (CRP) levels (OR, 1.11; 95% CI, 1.05-1.17; P = 0.013), T lymphocyte count (OR, 0.82; 95% CI, 0.69-0.93; P = 0.011), and interleukin-6 (IL-6) levels (OR, 1.17; 95% CI, 1.08-1.23; P = 0.003) were independently associated with the development of ARDS in critically ill patients. Conclusions: Our study identified age, CRP, T lymphocyte count, and IL-6 as independent predictors of ARDS in critically ill patients admitted to the ICU. These findings highlight the importance of monitoring these parameters in critically ill patients to identify those at high risk of developing ARDS. Early recognition and intervention based on these risk factors may improve patient outcomes in the ICU setting. Further prospective studies are warranted to validate these results and develop a reliable predictive model for ARDS in critically ill patients.

A Case of Takotsubo Syndrome in a Smoker-Epileptic Patient With Rhinovirus Pneumonia in the Intensive Care Unit: Could the InterTAK Criteria Be Useful?

Takotsubo syndrome (TS) is an acute cardiac dysfunction that typically presents hypokinesis of the apical segment of the left ventricle beyond a single coronary artery territory. The pathological mechanisms of TS remain unclear, and several possible theories have been postulated, including catecholamine excess, coronary artery spasm, microvascular dysfunction, and metabolic disturbances. Based on the etiology, a primary and secondary form is distinguished. In primary TS, acute cardiac symptoms are the primary reason for seeking acute medical care. In secondary TS, the syndrome occurs in patients already hospitalized for a medical or surgical condition. The clinical conditions most frequently associated with TS are respiratory pathologies, sepsis, neurological disease, endocrine disease, and psychiatric pathologies. The incidence of TS is poorly studied in the critically ill patient setting; furthermore, it is very difficult to determine its incidence, duration, and progression from the current literature. We present the clinical case of a secondary TS in a smoker patient with a history of epilepsy, hospitalized in the ICU for respiratory failure due to viral pneumonia, complicated with bronchospasm, highlighting the diagnostic difficulties in critically ill patients, the presence of multiple trigger factors, and the need to perform an early diagnosis for patient survival.

Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study.

BACKGROUND: This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir. METHODS: A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations. RESULTS: The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir. CONCLUSIONS: PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.

Effect of intravenous thiamine administration on critically ill patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND &AIMS: Thiamine is an essential micronutrient for energy metabolism. Thiamine deficiency is frequently observed in critically ill patients. However, the effect of thiamine administration is unclear in critically ill patients. METHODS: We conducted a systematic review and meta-analysis. To identify randomized controlled trials on the effect of thiamine administration in critically ill patients, a literature search was conducted in MEDLINE, CENTRAL, and ICHUSHI databases from inception to April 2023. Pooled effect estimates were calculated about mortality as the primary outcome and shock duration, lactate level, Sequential Organ Failure Assessment (SOFA) score, delirium, length of mechanical ventilation, length of intensive care unit (ICU) stay, infection rate, all adverse events, and Short-Form Health Survey (SF-36) as the secondary outcomes. The certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Overall, 35 studies (3494 patients) were included. Evidence suggested that thiamine administration resulted in little to no difference in mortality (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.75 to 1.06; Low CoE); however, thiamine administration may reduce shock duration (mean difference [MD], -11.43 h; 95% CI, -20.16 to -2.69 h; Low CoE), lactate level (MD, -0.34 mmol/L; 95% CI, -0.63 to -0.05 mmol/L; Low CoE), and SOFA score (MD, -1.29; 95% CI, -1.91 to -0.66; Low CoE). Conversely, thiamine administration resulted in a slight increase in the length of ICU stay (MD, 0.40 days; 95% CI, 0.01-0.79 days; High CoE). CONCLUSIONS: Although thiamine administration may reduce shock state, it may not reduce mortality, and slightly increases the length of ICU stay.

Effects of high-fat, low-carbohydrate enteral nutrition in critically ill patients: A systematic review with meta-analysis.

BACKGROUND & AIMS: High-fat, low-carbohydrate enteral nutrition has gained attention, with expectations of an improved respiratory condition, fewer complications, and lower mortality. The present study performed a systematic review and meta-analysis of randomized controlled trials to examine the effects of high-fat, low-carbohydrate enteral nutrition in critically ill adult patients. METHODS: We searched MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and ICHUSHI for randomized controlled trials comparing high-fat, low-carbohydrate enteral nutrition to standard enteral nutrition in critically ill adult patients who received enteral nutrition. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) mortality, length of ICU stay, length of mechanical ventilation, and adverse events of diarrhea and gastric residual volume. We examined the risk of bias using the Cochrane risk-of-bias tool for randomized trials version 2. We assessed the overall certainty of evidence based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Synthesis results were calculated with risk ratios and 95% confidence intervals using a Mantel-Haenszel random-effects model. RESULTS: Eight trials with 607 patients were included. The effects of high-fat, low-carbohydrate enteral nutrition on mortality did not significantly differ from those of standard enteral nutrition (62/280 [22.1%] vs. 39/207 [18.8%], risk ratios = 1.14, 95% confidence intervals 0.80 to 1.62, P = 0.47). No significant differences were observed in ICU mortality, ICU length of stay, diarrhea, or gastric residual volume between the two groups. However, high-fat, low-carbohydrate enteral nutrition was associated with a significantly shorter duration of mechanical ventilation (mean difference -1.72 days, 95% confidence intervals -2.93 to -0.50, P = 0.005). CONCLUSION: High-fat, low-carbohydrate enteral nutrition may not affect mortality, but may decrease the duration of mechanical ventilation in critically ill adult patients. Limitations include the small number of studies and potential for bias. Further research is needed to confirm these results and investigate effects on other outcomes and in a subgroup of patients requiring mechanical ventilation.

Enhancing Communication in Critically Ill Patients with a Tracheostomy: A Systematic Review of Evidence-Based Interventions and Outcomes.

Background: Tracheostomy, a common procedure performed in intensive care units (ICU), is associated with communication impairment and affects patient well-being. While prior research has focused on physiological care, there is a need to address communication needs and quality of life (QOL). We aimed to evaluate how different types of communication devices affect QOL, speech intelligibility, voice quality, time to significant events, clinical response and tolerance, and healthcare utilization in patients undergoing tracheostomy. Methods: Following PRISMA guidelines, a systematic review was conducted to assess studies from 2016 onwards. Eligible studies included adult ICU patients with a tracheostomy, comparing different types of communication devices. Data were extracted and synthesized to evaluate QOL, speech intelligibility, voice quality, time to significant events (initial communication device use, oral intake, decannulation), clinical response and tolerance, and healthcare utilization and facilitators/barriers to device implementation. Results: Among 9,228 studies screened, 8 were included in the review. Various communication devices were employed, comprising both tracheostomy types and speaking valves, highlighting the multifaceted nature of interventions. Quality of life improvements were observed with voice restoration interventions, but challenges such as speech intelligibility impairments were noted. The median time for initial communication device usage post-intervention was 11.4 ± 5.56 days. The median duration of speech tolerance ranged between 30-60 minutes to 2-3 hours across different studies. Complications such as air trapping or breathing difficulties were reported in 15% of cases. Additionally, the median ICU length of stay post-intervention was 36.5 days. Key facilitators for device implementation included early intervention, while barriers ranged from service variability to physical intolerance issues. Conclusion: Findings demonstrate that various types of communication devices can significantly enhance the quality of life, speech intelligibility, and voice quality for patients undergoing tracheostomy, aligning with the desired outcomes of improved clinical response and reduced healthcare utilization. The identification of facilitators and barriers to device implementation further informs clinical practice, suggesting a tailored, patient-centered approach is crucial for optimizing the benefits of communication devices in this population.