scholarly journals Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260656
Author(s):  
Anne-Lise Bienvenu ◽  
Pierre Pradat ◽  
Alexandra Plesa ◽  
Vincent Leclerc ◽  
Vincent Piriou ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Critically Ill ◽  
Sofa Score ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Multicenter Cohort Study ◽  
Large Variability ◽  
Optimal Drug ◽  
The Impact

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

Evaluation of Intravenous Phenobarbital Pharmacokinetics in Critically Ill Patients With Brain Injury

2022 ◽  
Author(s):  
Seyedeh Sana Khezrnia ◽  
Bita Shahrami ◽  
Mohammad Reza Rouini ◽  
Atabak Najafi ◽  
Hamid Reza Sharifnia ◽  
...  
Keyword(s):  
Brain Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Population ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Uv Detector ◽  
Therapeutic Goals ◽  
The Impact

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.

scholarly journals Pharmacokinetics of Daptomycin in Critically Ill Pediatric Patients

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Charalampos Antachopoulos ◽  
Stavroula Ilia ◽  
Paschalis Kadiltzoglou ◽  
Eirini Baira ◽  
Aristides Dokoumetzidis ◽  
...  
Keyword(s):  
Critically Ill ◽  
Drug Exposure ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Burn Patients ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Optimal Drug

ABSTRACT The pharmacokinetics of daptomycin (10 mg/kg once daily) was studied in 4 critically ill pediatric patients aged 8 to 14 yrs. The area under the concentration-time curve from time zero to infinity (AUC 0–∞ ) of plasma concentrations on day 1 ranged between 123.8 to 663.9 μg · h/ml, with lower values observed in septic and burn patients; clearance ranged from 15.1 to 80.7 ml/h/kg. Higher-than-recommended doses of daptomycin may be needed in septic children to ensure optimal drug exposure. Interpatient variability may suggest a role for therapeutic drug monitoring.

scholarly journals Model-Optimized Fluconazole Dose Selection for Critically Ill Patients Improves Early Pharmacodynamic Target Attainment without the Need for Therapeutic Drug Monitoring

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Indy Sandaradura ◽  
Jessica Wojciechowski ◽  
Deborah J. E. Marriott ◽  
Richard O. Day ◽  
Sophie Stocker ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Dose Selection ◽  
Dose Individualization

ABSTRACT Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study. The objective of this study was to evaluate fluconazole drug exposure in critically ill patients comparing a novel model-optimized dose selection method with established approaches over a standard 14-day (336-h) treatment course. Target attainment was evaluated in a representative population of 1,000 critically ill adult patients for (i) guideline dosing (800-mg loading and 400-mg maintenance dosing adjusted to renal function), (ii) guideline dosing followed by therapeutic drug monitoring (TDM)-guided dose adjustment, and (iii) model-optimized dose selection based on patient factors (without TDM). Assuming a MIC of 2 mg/liter, free fluconazole 24-h area under the curve (fAUC24) targets of ≥200 mg · h/liter and <800 mg · h/liter were used for assessment of target attainment. Guideline dosing resulted in underexposure in 21% of patients at 48 h and in 23% of patients at 336 h. The TDM-guided strategy did not influence 0- to 48-h target attainment due to inherent procedural delays but resulted in 37% of patients being underexposed at 336 h. Model-optimized dosing resulted in ≥98% of patients meeting efficacy targets throughout the treatment course, while resulting in less overexposure compared with guideline dosing (7% versus 14%) at 336 h. Model-optimized dose selection enables fluconazole dose individualization in critical illness from the outset of therapy and should enable reevaluation of the comparative effectiveness of this drug in patients with severe fungal infections.

scholarly journals Suboptimal Dosing of Fluconazole in Critically Ill Patients: Time To Rethink Dosing

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Eline W. Muilwijk ◽  
Dylan W. de Lange ◽  
Jeroen A. Schouten ◽  
Roeland E. Wasmann ◽  
Rob ter Heine ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Therapeutic Drug ◽  
Open Label ◽  
Time Curve ◽  
Icu Patients ◽  
Unbound Fraction ◽  
Multicenter Observational Study ◽  
The Impact

ABSTRACT Fluconazole is frequently used for the treatment of invasive Candida infections in critically ill patients. However, alterations in renal functions might influence fluconazole clearance. Therefore, our objective was to study the impact of renal function on the population pharmacokinetics of fluconazole in critically ill patients with various degrees of renal function or undergoing continuous renal replacement therapy (CRRT). This was an open-label, multicenter observational study. Critically ill patients receiving fluconazole were included. Baseline and clinical data were collected. At days 3 and 7 of enrollment, blood samples were drawn for pharmacokinetic curves. Additionally, daily trough samples were taken. A nonlinear mixed-effects model was built, followed by Monte Carlo simulations for assessment of exposure to various dosages of fluconazole. Nineteen patients were included with a median age of 64.4 (range, 23 to 81) years and median weight of 82.0 (range, 44.0 to 119.5) kg. A linear two-compartment model best described fluconazole pharmacokinetics and demonstrated higher clearance than expected in critically ill patients. Simulations showed that daily dosages of 600 mg and 800 mg are needed for intensive care unit (ICU) patients with normal renal function and patients on CRRT, respectively, to achieve the EUCAST-recommended target fAUC (area under the concentration-time curve for the free, unbound fraction of the drug)/MIC ratio of 100. In conclusion, fluconazole clearance is highly variable in ICU patients and is strongly dependent on renal function and CRRT. Trough concentrations correlated well with the AUC, opening up opportunities for tailored dosing using therapeutic drug monitoring. We recommend doses of 400 mg for patients with poor to moderate renal function, 600 mg for patients with adequate renal function, and 800 mg for patients treated with CRRT. (This study has been registered at ClinicalTrials.gov under identifier NCT02666716.)

scholarly journals Individualization of Piperacillin Dosing for Critically Ill Patients: Dosing Software To Optimize Antimicrobial Therapy

2014 ◽  
Vol 58 (7) ◽  
pp. 4094-4102 ◽  
Author(s):  
T. W. Felton ◽  
J. A. Roberts ◽  
T. P. Lodise ◽  
M. Van Guilder ◽  
E. Boselli ◽  
...  
Keyword(s):  
Linear Regression ◽  
Creatinine Clearance ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Volume Of Distribution ◽  
Drug Clearance ◽  
Dose Optimization ◽  
Optimization Software ◽  
The Impact

ABSTRACTPiperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated anr2of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.

scholarly journals Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

2020 ◽  
Vol 8 (3) ◽  
pp. 415 ◽  
Author(s):  
Stefan Felix Ehrentraut ◽  
Stefan Muenster ◽  
Stefan Kreyer ◽  
Nils Ulrich Theuerkauf ◽  
Christian Bode ◽  
...  
Keyword(s):  
Renal Function ◽  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Plasma Levels ◽  
Therapeutic Drug ◽  
The Right ◽  
The Impact ◽  
Current Guidelines

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

scholarly journals Personalized Piperacillin Dosing for the Critically Ill: A Retrospective Analysis of Clinical Experience with Dosing Software and Therapeutic Drug Monitoring to Optimize Antimicrobial Dosing

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 667
Author(s):  
Ute Chiriac ◽  
Daniel C. Richter ◽  
Otto R. Frey ◽  
Anka C. Röhr ◽  
Sophia Helbig ◽  
...  
Keyword(s):  
Septic Shock ◽  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Severe Infections ◽  
Sepsis And Septic Shock

Optimization of antibiotic dosing is a treatment intervention that is likely to improve outcomes in severe infections. The aim of this retrospective study was to describe the therapeutic exposure of steady state piperacillin concentrations (cPIP) and clinical outcome in critically ill patients with sepsis or septic shock who received continuous infusion of piperacillin with dosing personalized through software-guided empiric dosing and therapeutic drug monitoring (TDM). Therapeutic drug exposure was defined as cPIP of 32–64 mg/L (2–4× the ‘MIC breakpoint’ of Pseudomonas aeruginosa). Of the 1544 patients screened, we included 179 patients (335 serum concentrations), of whom 89% achieved the minimum therapeutic exposure of >32 mg/L and 12% achieved potentially harmful cPIP > 96 mg/L within the first 48 h. Therapeutic exposure was achieved in 40% of the patients. Subsequent TDM-guided dose adjustments significantly enhanced therapeutic exposure to 65%, and significantly reduced cPIP > 96 mg/L to 5%. Mortality in patients with cPIP > 96 mg/L (13/21; 62%) (OR 5.257, 95% CI 1.867–14.802, p = 0.001) or 64–96 mg/L (30/76; 45%) (OR 2.696, 95% CI 1.301–5.586, p = 0.007) was significantly higher compared to patients with therapeutic exposure (17/72; 24%). Given the observed variability in critically ill patients, combining the application of dosing software and consecutive TDM increases therapeutic drug exposure of piperacillin in patients with sepsis and septic shock.

scholarly journals Nutritional Assessment in the Critically Ill Patients

2020 ◽  
Author(s):  
Elham Bagheri ◽  
Farzaneh Hematian ◽  
Mandana Izadpanah ◽  
Mahbobeh Rashidi
Keyword(s):  
Critically Ill ◽  
Sofa Score ◽  
Critically Ill Patients ◽  
Nutritional Assessment ◽  
Apache Ii ◽  
Nutritional Risk ◽  
Apache Ii Score ◽  
Number Of Patients ◽  
Study Results ◽  
The Impact

Background: Malnutrition is a prevalent complication among critically ill patients. It has very detrimental effects on the patients' clinical course. This study aimed to investigate the impact of nutrition in the intensive care unit (ICU) patients. Methods: In this epidemiologic-analytic study conducted in the surgical ICU of Imam Khomeini hospital, Ahvaz, Iran, 34 patients were selected and divided into two groups. The first group of patients received the appropriate nutrition. The second group received an inappropriate diet, and the nutritional risk was evaluated according to the modified- Nutrition Risk in Critically ill (m-NUTRIC) score. The energy was calculated by using 25 Kcal/kg, also the two groups were compared in terms of ICU mortality, ICU stays, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II Scoring, and the Sequential Organ Failure Assessment (SOFA) Score. Results: Baseline data, such as APACHE II score and mean age, except sex, were not significantly different between the two groups. In this study, results were toward shorter ICU stay, less mortality, and better SOFA score in the group receiving appropriate nutrition compared to the other group. However, due to the low number of patients, no significant differences were observed in the two groups. Conclusion: Our data suggest that nutritional support should be considered as an essential part of the medication during critical illness.

scholarly journals Outcomes of non-COVID-19 critically ill patients during the COVID-19 pandemic

2021 ◽  
Author(s):  
Răzvan Bologheanu ◽  
Mathias Maleczek ◽  
Daniel Laxar ◽  
Oliver Kimberger
Keyword(s):  
Intensive Care ◽  
Length Of Stay ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Medical Specialty ◽  
Routine Care ◽  
Treatment Pathways ◽  
Icu Length Of Stay ◽  
Matched Study ◽  
The Impact

Summary Background Coronavirus disease 2019 (COVID-19) disrupts routine care and alters treatment pathways in every medical specialty, including intensive care medicine, which has been at the core of the pandemic response. The impact of the pandemic is inevitably not limited to patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their outcomes; however, the impact of COVID-19 on intensive care has not yet been analyzed. Methods The objective of this propensity score-matched study was to compare the clinical outcomes of non-COVID-19 critically ill patients with the outcomes of prepandemic patients. Critically ill, non-COVID-19 patients admitted to the intensive care unit (ICU) during the first wave of the pandemic were matched with patients admitted in the previous year. Mortality, length of stay, and rate of readmission were compared between the two groups after matching. Results A total of 211 critically ill SARS-CoV‑2 negative patients admitted between 13 March 2020 and 16 May 2020 were matched to 211 controls, selected from a matching pool of 1421 eligible patients admitted to the ICU in 2019. After matching, the outcomes were not significantly different between the two groups: ICU mortality was 5.2% in 2019 and 8.5% in 2020, p = 0.248, while intrahospital mortality was 10.9% in 2019 and 14.2% in 2020, p = 0.378. The median ICU length of stay was similar in 2019: 4 days (IQR 2–6) compared to 2020: 4 days (IQR 2–7), p = 0.196. The rate of ICU readmission was 15.6% in 2019 and 10.9% in 2020, p = 0.344. Conclusion In this retrospective single center study, mortality, ICU length of stay, and rate of ICU readmission did not differ significantly between patients admitted to the ICU during the implementation of hospital-wide COVID-19 contingency planning and patients admitted to the ICU before the pandemic.

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