A Comprehensive Review of Chloride Management in Critically Ill Patients.

Chloride, often overshadowed in electrolyte management, emerges as a crucial player in the physiological intricacies of critically ill patients. This comprehensive review explores the multifaceted aspects of chloride, ranging from its significance in cellular homeostasis to the consequences of dysregulation in critically ill patients. The pathophysiology of hyperchloremia and hypochloremia is dissected, highlighting their intricate impact on acid-base balance, renal function, and cardiovascular stability. Clinical assessment strategies, including laboratory measurements and integration with other electrolytes, lay the foundation for targeted interventions. Consequences of dysregulated chloride levels underscore the need for meticulous management, leading to an exploration of emerging therapies and interventions. Fluid resuscitation protocols, the choice between crystalloids and colloids, the role of balanced solutions, and individualized patient approaches comprise the core strategies in chloride management. Practical considerations, such as monitoring and surveillance, overcoming implementation challenges, and embracing a multidisciplinary approach, are pivotal in translating theoretical knowledge into effective clinical practice. As we envision the future, potential impacts on critical care guidelines prompt reflections on integrating novel therapies, individualized approaches, and continuous monitoring practices. In conclusion, this review synthesizes current knowledge, addresses practical considerations, and envisions future directions in chloride management for critically ill patients. By embracing a holistic understanding, clinicians can navigate the complexities of chloride balance, optimize patient outcomes, and contribute to the evolving landscape of critical care medicine.

Thiamine administration may increase survival benefit in critically ill patients with myocardial infarction.

Background: Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients. Methods: The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out. Results: This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results. Conclusion: Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

Terapia medico nutricional en pacientes que reciben terapia de oxigenación por membrana extracorpórea: conocimiento en progreso / Medical nutrition therapy in patients receiving extracorporeal membrane oxygenation: knowledge in progress

Resumen El soporte nutricional (SN) en pacientes adultos que reciben terapia de oxigenación por membrana extracorpórea (ECMO, extracorporeal membrane oxygenation) es controvertido. Si bien existen guías para el SN en pacientes pediátricos con ECMO, en adultos no se cuenta con estos lineamientos para el uso, tipo, ruta y momento de la terapia nutricional. En pacientes críticamente enfermos es bien sabido que la nutrición enteral (NE) temprana es beneficiosa, no obstante existe la posibilidad de que en pacientes con ECMO la NE temprana condicione complicaciones gastrointestinales. Asimismo, no se han establecido metas calóricas, proteicas y dosis o tipos de micronutrimentos que usar para esta población en específico, siendo un reto para el clínico encargado de brindar el SN. Aunado a esto los pacientes con ECMO son algunos de los más gravemente enfermos en las unidades de cuidados intensivos, donde la desnutrición se asocia con una mayor morbilidad y mortalidad. En cuanto al uso de nutrición parenteral (NP), no se tiene descrito si implica riesgo de falla en el circuito al momento de introducir lípidos al oxigenador. Por lo anterior es imperativa una correcta evaluación e intervención nutricional específica, realizada por expertos en el tema para mejorar el pronóstico y la calidad de vida en esta población, siendo un objetivo primordial en los cuidados de los pacientes adultos que reciben terapia de ECMO.

Abstract Nutritional support in adult patients receiving extracorporeal membrane oxygenation (ECMO) therapy is controversial. Although there are guidelines for the NS (Nutritional support) in pediatric patients with ECMO, in adults these guidelines are not available for the use, type, route and timing of nutritional therapy. In critically ill patients it is well known that early enteral nutrition is beneficial, however there is the possibility that in patients with ECMO early enteral nutrition leads to gastrointestinal complications. Likewise, there have not been established caloric targets, proteins and doses or types of micronutrients to use for this specific population being a challenge for the clinician. In addition, patients with ECMO are some of the most seriously ill in intensive care units, where malnutrition is associated with increased morbidity and mortality. Regarding the use of parenteral nutrition (NP) it has not been described if it implies a risk of circuit failure at the time of introducing lipids to the oxygenator. Therefore, a correct evaluation and specific nutritional intervention by experts in the field is imperative to improve the prognosis and quality of life in this population, which is a primary goal in the care of adult patients receiving extracorporeal membrane oxygen.

Medical nutrition therapy in patients receiving extracorporeal membrane oxygenation: knowledge in progress.

Nutritional support in adult patients receiving extracorporeal membrane oxygenation (ECMO) therapy is controversial. Although there are guidelines for the NS (Nutritional support) in pediatric patients with ECMO, in adults these guidelines are not available for the use, type, route and timing of nutritional therapy. In critically ill patients it is well known that early enteral nutrition is beneficial, however there is the possibility that in patients with ECMO early enteral nutrition leads to gastrointestinal complications. Likewise, there have not been established caloric targets, proteins and doses or types of micronutrients to use for this specific population being a challenge for the clinician. In addition, patients with ECMO are some of the most seriously ill in intensive care units, where malnutrition is associated with increased morbidity and mortality. Regarding the use of parenteral nutrition (NP) it has not been described if it implies a risk of circuit failure at the time of introducing lipids to the oxygenator. Therefore, a correct evaluation and specific nutritional intervention by experts in the field is imperative to improve the prognosis and quality of life in this population, which is a primary goal in the care of adult patients receiving extracorporeal membrane oxygen.

El soporte nutricional (SN) en pacientes adultos que reciben terapia de oxigenación por membrana extracorpórea (ECMO, extracorporeal membrane oxygenation) es controvertido. Si bien existen guías para el SN en pacientes pediátricos con ECMO, en adultos no se cuenta con estos lineamientos para el uso, tipo, ruta y momento de la terapia nutricional. En pacientes críticamente enfermos es bien sabido que la nutrición enteral (NE) temprana es beneficiosa, no obstante existe la posibilidad de que en pacientes con ECMO la NE temprana condicione complicaciones gastrointestinales. Asimismo, no se han establecido metas calóricas, proteicas y dosis o tipos de micronutrimentos que usar para esta población en específico, siendo un reto para el clínico encargado de brindar el SN. Aunado a esto los pacientes con ECMO son algunos de los más gravemente enfermos en las unidades de cuidados intensivos, donde la desnutrición se asocia con una mayor morbilidad y mortalidad. En cuanto al uso de nutrición parenteral (NP), no se tiene descrito si implica riesgo de falla en el circuito al momento de introducir lípidos al oxigenador. Por lo anterior es imperativa una correcta evaluación e intervención nutricional específica, realizada por expertos en el tema para mejorar el pronóstico y la calidad de vida en esta población, siendo un objetivo primordial en los cuidados de los pacientes adultos que reciben terapia de ECMO.

Jumping into the future: overcoming pharmacokinetic/pharmacodynamic hurdles to optimize the treatment of severe difficult to treat-Gram-negative infections with novel beta-lactams.

INTRODUCTION: The choice of best therapeutic strategy for difficult-to-treat resistance (DTR) Gram-negative infections currently represents an unmet clinical need. AREAS COVERED: This review provides a critical reappraisal of real-world evidence supporting the role of pharmacokinetic/pharmacodynamic (PK/PD) optimization of novel beta-lactams in the management of DTR Gram-negative infections. The aim was to focus on prolonged and/or continuous infusion administration, penetration rates into deep-seated infections, and maximization of PK/PD targets in special renal patient populations. Retrieved findings were applied to the three most critical clinical scenarios of Gram-negative resistance phenotypes (i.e. carbapenem-resistant Enterobacterales; difficult-to-treat resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii). EXPERT OPINION: Several studies supported the role of PK/PD optimization of beta-lactams in the management of DTR Gram-negative infections for both maximizing clinical efficacy and preventing resistance emergence. Optimizing antimicrobial therapy with novel beta-lactams based on the so called 'antimicrobial therapy puzzle' PK/PD concepts may represent a definitive jump into the future toward a personalized patient management of DTR Gram negative infections. Establishing a dedicated and coordinated multidisciplinary team and implementing a real-time TDM-guided personalized antimicrobial exposure optimization of novel beta-lactams based on expert clinical pharmacological interpretation, could represent crucial cornerstones for the proper management of DTR Gram-negative infections.

The Effects of Glutamine Supplementation on Reducing Mortality and Morbidity among Burn Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Glutamine (GLN) has been proven to improve the prognosis of severely burned patients. GLN supplementation in critical illness has gained extreme popularity among researchers over the years, and its safety and efficacy are still under question. Therefore, we aim to study the role of GLN supplements in decreasing mortality, length of hospitalization (LOH), and infection in severely burned patients. PRISMA guidelines were used to design and conduct this systematic review. MEDLINE, Cochrane, and EMBASE databases were used to search for randomized controlled trials (RCTs) in January 2022. In order to assist in the search, MeSH terms such as burn injury, GLN, and RCT were used. As a result of reviewing the literature, 1112 publications were found. We included only 7 RCTs after implanting our inclusion criteria. There were 328 patients enrolled in the study, with 166 patients (50.61%) were allocated to GLN supplementation and 162 patients in the control groups (49.39%). The risk of infection was significantly lower among patients who received GLN supplementation than those in the control groups (RR = 0.41, 95% CI, 0.18 to 0.92, p = 0.030). The risk of death was significantly lower among GLN-receiving patients compared to non-GLN-receiving patients (RR = 0.09, 95% CI, 0.01 to 0.63, p = 0.016). GLN supplementation has been linked to lower hospital mortality and infection-related morbidity in burn patients. Furthermore, larger-scale and higher-quality studies are needed to assess whether there are any statistically and clinically significant changes.

Effects of supplementation with low-dose group B vitamins on clinical and biochemical parameters in critically ill patients with COVID-19: a randomized clinical trial.

BACKGROUND: : This study aimed to check the effect of supplementation with low-dose group B vitamins on clinical and biochemical parameters on patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHOD: : This double-blind, randomized clinical trial was carried out on 85 critically ill patients with COVID-19. All patients received high protein prescriptions of 30 kcal/kg/d by enteral nutrition. The intervention group (n = 40) received vitamin B complex, including thiamine (10 mg), riboflavin (4 mg), nicotinamide (40 mg), and dexpanthenol (6 mg). The control group received similar nutritional supports, except for group B vitamins. Assessments were carried out at baseline and after 2 weeks of intervention. RESULTS: : Vitamin B supplementation had no effects on the biochemical and pathological parameters including kidney function, arterial blood gas parameters, Glasgow coma scale, cell blood count, and serum electrolytes of the intervention group compared with the control group. The 30-day mortality was insignificantly lower in the intervention group than in the control group (83.3% against 96.1%, P = 0.07). CONCLUSIONS: The mortality rate of patients with COVID-19 might be improved by low-dose vitamin B supplementation.

Vitamin D Supplementation in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials.

Randomized controlled trials (RCTs) have reported conflicting outcomes with the use of vitamin D in critically ill patients. With reporting of newer RCTs, we conducted this updated meta-analysis. Electronic databases were searched for RCTs comparing vitamin D with placebo in critically ill patients admitted to the intensive care unit (ICU). A random-effects meta-analysis was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (CI). Eleven RCTs with a total of 2,187 patients (vitamin D: n = 1,120; placebo: n = 1,067) were included. Vitamin D when compared to placebo was associated with the decreased duration of mechanical ventilation (SMD = -0.50; 95% CI = [-0.97, -0.03]; p = 0.04) and ICU stay (SMD = -0.60; 95% CI = [-1.03, -0.16]; p = 0.007) without any difference in the mortality (RR = 0.85; 95% CI = [0.68, 1.04]; p = 0.12) and length of hospital stay (SMD = -0.21; 95% CI = (-0.51, 0.09); p = 0.18]. Subgroup analysis showed that parenteral vitamin D may reduce the risk of mortality (RR = 0.54; 95% CI = [0.35, 0.83], p = 0.005). Vitamin D supplementation in critically ill patients decreases the duration of mechanical ventilation and ICU stay. Further studies should identify specific groups of patients who will derive the most benefit from vitamin D supplementation.

Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.

Differences in pharmacokinetics/pharmacodynamics (PK/PD) target attainment are rarely considered when antifungals are switched in critically ill patients. This study intends to explore whether the antifungal de-escalation treatment strategy and the new intermittent dosing strategy of echinocandins in critically ill patients are able to achieve the corresponding PK/PD targets. The published population PK models of antifungals in critically ill patients and a public data set from the MIMIC-III database (n = 662) were employed to evaluate PK/PD target attainment of different dosing regimens of antifungals. Cumulative fraction of response (CFR) was calculated for each dosing regimen. Most guideline-recommended dosing regimens of fluconazole and voriconazole could achieve target exposure as de-escalation treatment in critically ill patients. For initial echinocandin treatment, achievement of the target exposure decreased as body weight increased, and the intermittent dosing strategy had a slightly higher CFR value in most simulations compared to conventional dosing strategy. For Candida albicans and Candida glabrata infection, caspofungin at the lowest dose achieved a CFR of >90%, while micafungin or anidulafungin required almost the highest doses simulated in this study to achieve the same effect. None of the echinocandins other than 150 mg every 24 h (q24h) or 200 mg q48h of caspofungin achieved the target CFR for Candida parapsilosis infection. These findings support the guideline-recommended dose of triazoles for antifungal de-escalation treatment and confirm the insufficient dosage of echinocandins in critically ill patients, indicating that a dosing regimen based on body weight or intermittent dosing of echinocandins may be required.

Serum micronutrient levels in critically ill patients receiving continuous renal replacement therapy: A prospective, observational study.

BACKGROUND: Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) may deplete micronutrient levels. Patients are also at risk for micronutrient depletion due to underlying illness(s), poor nutrient intake prior to intensive care unit (ICU) admission and/or increased requirements. We determined vitamin and trace element status before, during and after CRRT in critically ill patients. METHODS: This prospective observational study performed in mixed medical and surgical ICU patients. Serial serum vitamin B6 and vitamin C concentrations were measured by HPLC and folic acid by ECLIA. Serum chromium, copper, selenium, and zinc were measured using ICP-MS. Serum ceruloplasmin was measured by the Erel method. RESULTS: Fifty adult ICU patients with AKI were recruited. The median APACHE II score on ICU admission was high at 24.0 (6.0-33.0). The median days on CRRT was 2.0 (2.0-4.0) days. At baseline (within 10-15 minutes of CRRT initiation), serum vitamin C, selenium and zinc were below normal. Serum vitamin B6 levels at 72 hours on CRRT were significantly lower than at 24 hours (p = 0.011). Serum vitamin C values fell significantly at 24 and 72 hours during CRRT (p = 0.030 and p = 0.001), respectively, and remained low 24 and 48 hours after CRRT was stopped (p = 0.021). At baseline and during CRRT, 96% of participants had at least two or more micronutrient levels below the normal range. CONCLUSION: Serum vitamin C, selenium and zinc concentrations were below the normal range at baseline. CRRT was associated with a significant further decrease in levels of vitamin C, selenium and zinc.

Therapeutic drug monitoring of meropenem and pharmacokinetic-pharmacodynamic target assessment in critically ill pediatric patients from a prospective observational study.

OBJECTIVES: To compare the unbound plasma meropenem concentrations at mid-dosing intervals (Cmid, 50%fT), end-dosing intervals (Ctrough, 100%fT), and proportions of patients achieving 50%fT and 100%fT above minimum inhibitory concentration (MIC) (50%fT>MIC and 100%fT>MIC) between extended infusion (EI) and intermittent bolus (IB) administration in a therapeutic drug monitoring (TDM) program in children. METHODS: A prospective observational study was conducted in children aged 1 month to 18 years receiving meropenem every 8 hours by either EI or IB. Meropenem Cmid, Ctrough, and proportions of patients achieving 50%fT>MIC and 100%fT>MIC were compared. RESULTS: TDM data from 72 patients with a median age (interquartile range [IQR]) of 12 months (3-37) were used. Meropenem dose was 120 and 60 mg/kg/day in EI and IB groups, respectively. Geometric mean (95% confidence interval [CI]) Cmid of EI versus IB was 17.3 mg/L (13.7-21.8) versus 3.4 mg/L (1.7-6.7) (P <0.001). Geometric mean (95% CI) Ctrough of EI versus IB was 2.3 mg/L (1.6-3.4) versus 0.8 mg/L (0.4-1.5) (P=0.005). Greater proportions of patients achieving 50%fT>MIC and 100%fT>MIC were observed in the EI group. CONCLUSIONS: A meropenem dose of 20 mg/kg/dose given by IB should not be used in critically ill children, even if they are not suspected of having a central nervous system infection. A dose of 40 mg/kg/dose given by EI resulted in higher Cmid, Ctrough, and proportions of patients achieving 50%fT>MIC and 100%fT>MIC.

Modelled Target Attainment after Temocillin Treatment in Severe Pneumonia: Systemic and Epithelial Lining Fluid Pharmacokinetics of Continuous versus Intermittent Infusions.

The objective of this article is to describe the population pharmacokinetics (PK) of temocillin administered via continuous infusion (CI) versus intermittent infusion (II) in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Thirty-two mechanically ventilated patients who were treated for pneumonia with 6 g of temocillin daily for in vitro sensitive pathogens were assigned to either the II (2 g every 8 h over 0.5 h) or the CI (6 g over 24 h after a loading dose of 2 g) group. A population pharmacokinetic model was developed using unbound plasma, and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. The area under the concentration-time curve from 0 to 24 h (AUC0-24) ELF/plasma penetration ratio was 0.73, at steady state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed that for the minimal pharmacodynamic (PD) targets of 50% T > 1× MIC (II group) and 100% T > 1× MIC (CI group), PK/PD breakpoints were 4 mg/L in plasma and 2 mg/L in ELF and 4 mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with creatinine clearance (CLCR) < 60 mL/min/1.73 m2. While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in the case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia.

Effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids, inflammation, and clinical outcomes in critically ill patients: A systematic review and meta-analysis.

BACKGROUND: Although some studies have explored the relationships between dietary fiber (DF) supplement and gut barrier function, changes of gut microbiota, and clinical outcomes in critically ill patients, the results were not consistent. OBJECTIVE: The purpose was to explore the effect of DF on gut barrier function, gut microbiota, short-chain fatty acids (SCFAs), inflammation, and clinical outcomes in critically ill patients. METHODS: A search was performed through five databases from inception to July 12, 2021. Data were expressed as mean difference (MD) or odds ratio (OR) with CI. RESULTS: Twenty-one studies involving 2084 critically ill patients were included. There was a significant reduction in intestinal permeability, demonstrated by lactulose/rhamnose ratio (MD, -0.04; 95% CI, -0.08 to -0.00; P = 0.03) on day 8, C-reactive protein on day 14 (MD, -36.66; 95% CI, -44.40 to -28.93; P < 0.001) and duration of hospital stay (MD, -3.16; 95% CI, -5.82 to -0.49; P < 0.05) after DF supplement. There were no significant differences in SCFA levels, duration of mechanical ventilation, and mortality between two groups. However, subgroup analysis results indicated significant decreases in duration of hospital stay and risk of mortality were seen in the subgroups with a supplementary fiber dose ≥20 g/day (MD, -5.62 [95% CI, -8.04 to -3.21; P < 0.0001]; OR, 0.18 [95% CI, 0.06-0.57; P = 0.004]), as well as in the medical intensive care unit (MD, -4.77 [95% CI, -7.48 to -2.07; P < 0.01]; OR, 0.13 [95% CI, 0.03-0.65; P < 0.05]). CONCLUSIONS: DF may improve gut barrier function, modulate intestinal microbiota, decrease systemic inflammatory response, and advance clinical outcomes in critically ill patients.

An evidence-based multidisciplinary approach focused at creating algorithms for targeted therapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales in critically ill adult patients.

INTRODUCTION: Prompt implementation of appropriate targeted antibiotic therapy representsa valuable approach in improving clinical and ecological outcome in critically septic patients. Thismultidisciplinary opinion article aims to develop evidence-based algorithms for targeted antibiotictherapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales,which are among the most common pathogens associated with these conditions. AREAS COVERED: A multidisciplinary team of four experts had several rounds of assessment for developingalgorithms devoted to targeted antimicrobial therapy of IVACs caused by Enterobacterales.A literature search was performed on PubMed-MEDLINE (until March 2021) to provide evidence forsupporting therapeutic choices. Quality and strength of evidence was established according toa hierarchical scale of the study design. Six different algorithms with associated recommendations concerning therapeutic choice and dosing optimization were suggested according to the susceptibilitypattern of Enterobacterales: multi-susceptible, extended-spectrum beta-lactamase (ESBL)-producing,AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and metallo-beta-lactamase (MBL)-producing Enterobacterales. EXPERT OPINION: The implementation of algorithms focused on prompt revision of antibiotic regimensguided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy ofnovel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and PK/PD optimization of antibiotic dosing regimens is strongly suggested.

Caloric Intake with High Ratio of Enteral Nutrition Associated with Lower Hospital Mortality for Patients with Acute Respiratory Distress Syndrome Using Prone Position Therapy.

Positioning patients in the prone position leads to reduced hospital mortality rates for those with severe acute respiratory distress syndrome (ARDS). What constitutes the optimal feeding strategy for prone patients with ARDS is controversial. We conducted a retrospective study that enrolled 110 prone patients with ARDS in two medical intensive care units (ICUs) from September 2015 to November 2018. Inclusion criteria were as follows: age ≥20 years, diagnosis of respiratory failure requiring mechanical ventilation, diagnosis of ARDS within 72 h of ICU admission, placement in a prone position within the first 7 days of ICU admission, and ICU stay of more than 7 days. Exclusion criteria were as follows: nil per os orders because of gastrointestinal bleeding or hemodynamic instability, and ventilator dependency because of chronic respiratory failure. The consecutive daily enteral nutrition(EN)/EN + parenteral nutrition(PN) ratio could predict hospital mortality rates within the first 7 days of admission when using generalized estimating equations (p = 0.013). A higher average EN/EN + PN ratio within the first 7 days predicted (hazard ratio: 0.97, confidence interval: 0.96-0.99) lower hospital mortality rates. To reduce hospital mortality rates, caloric intake with a higher EN ratio may be considered for patients in prone positions with ARDS.

Comprehensive versus standard care in post-severe acute kidney injury survivors, a randomized controlled trial.

BACKGROUND: Currently, there is a lack of evidence to guide optimal care for acute kidney injury (AKI) survivors. Therefore, post-discharge care by a multidisciplinary care team (MDCT) may improve these outcomes. This study aimed to demonstrate the outcomes of implementing comprehensive care by a MDCT in severe AKI survivors. METHODS: This study was a randomized controlled trial conducted between August 2018 to January 2021. Patients who survived severe AKI stage 2-3 were enrolled and randomized to be followed up with either comprehensive or standard care for 12 months. The comprehensive post-AKI care involved an MDCT (nephrologists, nurses, nutritionists, and pharmacists). The primary outcome was the feasibility outcomes; comprising of the rates of loss to follow up, 3-d dietary record, drug reconciliation, and drug alert rates at 12 months. Secondary outcomes included major adverse kidney events, estimated glomerular filtration rate (eGFR), and the amount of albuminuria at 12 months. RESULTS: Ninety-eight AKI stage 3 survivors were enrolled and randomized into comprehensive care and standard care groups (49 patients in each group). Compared to the standard care group, the comprehensive care group had significantly better feasibility outcomes; 3-d dietary record, drug reconciliation, and drug alerts (p < 0.001). The mean eGFR at 12 months were comparable between the two groups (66.74 vs. 61.12 mL/min/1.73 m2, p = 0.54). The urine albumin: creatinine ratio (UACR) was significantly lower in the comprehensive care group (36.83 vs. 177.70 mg/g, p = 0.036), while the blood pressure control was also better in the comprehensive care group (87.9% vs. 57.5%, p = 0.006). There were no differences in the other renal outcomes between the two groups. CONCLUSIONS: Comprehensive care by an MDCT is feasible and could be implemented for severe AKI survivors. MDCT involvement also yields better reduction of the UACR and better blood pressure control. Trial registration Clinicaltrial.gov: NCT04012008 (First registered July 9, 2019).

Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group.

BACKGROUND: The cumbersome program and the shortage of commercial solution hindered the regular application of regional citrate anticoagulation (RCA). It is urgent to simplify the protocol using only commercial preparations. The aim of this study was to explore the feasibility and efficacy of the modified protocol for continuous veno-venous hemofiltration (CVVH) in unselected critically ill patients. METHODS: A prospective cohort study was conducted in 66 patients who received a new protocol combining fixed citrate concentration with modified algorithm for supplements (i.e., fixed protocol), and compared the efficacy, safety and convenience for this group to a historical control group with a traditional protocol (n = 64), where citrate was titrated according to the circuit ionized calcium concentration (i.e., titrated protocol). The convenience was defined as the demand for monitoring test and dose adjustment of any supplement. RESULTS: The filter lifespan was 63.2 ± 16.1 h in the fixed group and 51.9 ± 17.7 h in the titrated group, respectively. Kaplan-Meier survival analysis demonstrated longer circuit lifetime for fixed group (log-rank, p = 0.026). The incidence of circuit clotting was lower in the fixed protocol (15.2% vs. 29.7% in the titrated protocol, p = 0.047). Moreover, compared with the titrated group, patients with fixed protocol had less demand for monitoring test and dose adjustment of any supplement (the number of times per person per day) (3.3 [IQR 2.3-4.5] vs. 5.7 [IQR 3.3-6.9], p = 0.001 and 1.9 [IQR 0.5-2.7] vs. 6.3 [IQR 4.2-7.9], p < 0.001; respectively). No new onset bleeding complications occurred in all patients. The overall incidence of suspected citrate accumulation was 4.6% and there was no difference between the two groups (p = 0.969), yet a lower rate of metabolic alkalosis was found in the fixed group (3.0% vs. 14.1%, p = 0.024). CONCLUSIONS: Our modified fixed citrate concentration protocol is feasible, safe and effective to enhance the circuit lifespan and the convenience of implementation while maintaining a similar safety when compared to the traditional protocol. Using only commercial preparations may be helpful for widespread application of RCA. TRIAL REGISTRATION: Clinicaltrials.gov. NCT02663960 . Registered 26 January 2016.

The Effect of Vitamin C on Pathological Parameters and Survival Duration of Critically Ill Coronavirus Disease 2019 Patients: A Randomized Clinical Trial.

Introduction: Vitamin C has been reported to have beneficial effects on patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of vitamin C supplementation on pathological parameters and survival duration of critically ill patients with COVID-19. Methods: This clinical trial was conducted on 120 hospitalized critically ill patients infected with COVID-19. The intervention group (n = 31) received one capsule of 500 mg of vitamin C daily for 14 days. The control group (n = 69) received the same nutrition except for vitamin C supplements. Measurement of pathological and biochemical parameters was performed at baseline and after 2 weeks of the intervention. Results: Following 2 weeks of vitamin C supplementation, the level of serum K was significantly lower in the patients compared with the control group (3.93 vs. 4.21 mEq/L, p < 0.01). Vitamin C supplementation resulted in a higher mean survival duration compared with that of the control group (8 vs. 4 days, p < 0.01). There was a linear association between the number of days of vitamin C intake and survival duration (B = 1.66, p < 0.001). The vitamin C supplementation had no effect on blood glucose, mean arterial pressure, arterial blood gas (ABG) parameters, Glasgow Coma Scale (GCS), kidney function, cell blood count (CBC), hemoglobin (Hb), platelet (Plt), partial thromboplastin time (PTT), albumin, hematocrit (Hct), and other serum electrolytes including sodium (Na), calcium, and phosphorus (P). Conclusion: The present study demonstrated the potential of vitamin C supplementation in enhancing the survival duration of critically ill patients with COVID-19. Clinical Trial Registration: https://www.irct.ir/trial/55074, identifier IRCT20151226025699N5.

Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy.

PURPOSES: To determine appropriate dosing of levofloxacin in critically ill patients receiving continuous renal replacement therapy (CRRT). METHODS: All necessary pharmacokinetic and pharmacodynamic parameters from critically ill patients were obtained to develop mathematical models with first order elimination. Levofloxacin concentration-time profiles were calculated to determine the efficacy based on the probability of target attainment (PTA) of AUC24h/MIC ≥50 for Gram-positive and AUC24h/MIC ≥125 for Gram-negative infections. A group of 5000 virtual patients was simulated and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the dose achieved target PTA at least 90% of the virtual patients. RESULTS: No conventional, FDA approved regimens achieved at least 90% of PTA for Gram-negative infection with Pseudomonas aeruginosa at MIC of 2 mg/L. The successful dose (1750 mg on day 1, then 1500 mg q 24 h) was far exceeded the maximum FDA-approved doses. For Gram-positive infections, a levofloxacin 750 mg q 24 h was sufficient to attain PTA target of ~90% at the MIC of 2 mg/L for Streptococcus pneumoniae. CONCLUSIONS: Levofloxacin cannot be recommended as an empiric monotherapy for serious Gram-negative infections in patients receiving CRRT due to suboptimal efficacy.