Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis

2015 ◽  
Vol 45 (6) ◽  
pp. 647-651 ◽  
Author(s):  
A.J. Brink ◽  
G.A. Richards ◽  
E.E.G. Lautenbach ◽  
N. Rapeport ◽  
V. Schillack ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Albumin Concentration

scholarly journals Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients

2018 ◽  
Vol 62 (6) ◽  
pp. e00242-18 ◽  
Author(s):  
Fekade B. Sime ◽  
Janine Stuart ◽  
Jenie Butler ◽  
Therese Starr ◽  
Steven C. Wallis ◽  
...  
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Central Venous Access ◽  
Plasma Concentrations ◽  
Parameter Estimates ◽  
Pharmacokinetic Data ◽  
Albumin Concentration ◽  
Data Set

ABSTRACT To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of i.v. posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if they were aged ≥18 years, central venous access was available, they were not pregnant, and they had not received prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 min. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled with the following characteristics: median age, 46 years (interquartile range [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR) pharmacokinetic parameter estimates were as follows: observed maximum concentration during sampling period (Cmax), 1,702 ng/ml (1,352 to 2,141 ng/ml); area under the concentration-time curve from zero to infinity (AUC0–∞), 17,932 ng · h/ml (13,823 to 27,905 ng · h/ml); clearance (CL), 16.8 liters/h (11.1 to 21.7 liters/h); and volume of distribution (V), 529.1 liters (352.2 to 720.6 liters). The V and CL were greater than 2-fold and the AUC0–∞ was 39% of the values reported for heathy volunteers. The AUC0–∞ was only 52% of the steady-state AUC0–24 reported for hematology patients. The median of estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163 ng/ml), which is within but close to the lower end of the previously recommended therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients compared to those in healthy volunteers and hematology patients.

Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification

2021 ◽  
Vol 20 (4) ◽  
pp. 81-94
Author(s):  
Artem V. Marukhov ◽  
Elena V. Murzina ◽  
Mikhail V. Zakharov ◽  
Genrikh A. Sofronov ◽  
Lyudmila V. Buryakova ◽  
...  
Keyword(s):  
Septic Shock ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Selective Adsorption ◽  
Plasma Concentrations ◽  
Blood Purification ◽  
Continuous Hemodiafiltration ◽  
Extracorporeal Blood ◽  
Extracorporeal Blood Purification ◽  
Extracorporeal Support

The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory. Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification. Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system. Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% TMIC for sensitive strains (MIC2 mg/L) and for intermediate resistance pathogens (2MIC8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem. Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.

Hydrocortisone vs Tocilizumab Effects on Cytokine Storm in Critically Ill Patients with COVID-19.

2020 ◽  
Author(s):  
Maria Vargas ◽  
Pasquale Buonanno ◽  
Carmine Iacovazzo ◽  
Gaetano Di Spigna ◽  
Daniela Spalletti ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Severe Pneumonia ◽  
Cytokine Storm ◽  
Tnf Α ◽  
Speed Up ◽  
The Impact ◽  
Late Stages

Abstract Introduction: Patients with severe pneumonia due COVID-19 are reported to have substantially lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines. In the late stages of COVID-19, cytokine storms are the mainly cause of disease progression and death. We performed a prospective observational study to evaluate the impact of tocilizumab and hydrocortisone on cytokine storm in critically ill patients with COVID-19.Methods: We included all adult patients with laboratory-confirmed COVID-19 infection and severe respiratory failure admitted to our ICU from March 10 to April 30. As therapeutic options, patients received tocilizumab od hydrocortisone. The primary end point was the evaluation of cytokine storm in terms of variation of the IL-6 and IL-6R, sgp130 and TNF-α concentrations during time to different treatment.Results: Eight patients received tocilizumab while 15 patients received hydrocortisone. IL-6 levels were lower in the hydrocortisone group with statistical significance was found at the days 2, 3, 8 and 9. The levels of IL-6R were lower during the days in the hydrocortisone group with statistical significance at days 1, 2, 3, 4, 5, 6, 8 and 10. Hydrocortisone group had higher levels of TNF-α at days 2, 3 and 4. The levels of sgo130 between tocilizumab and hydrocortisone groups were not statistically different during the days.Conclusions: In critically ill patients with severe COVID-19, the use of hydrocortisone allowed a better control of the cytokine storms, was further associated to less days of curarization, pronation and length of stay in ICU, and speed up the time to get negative RT-PCR swab.

scholarly journals Pharmacokinetic Optimisation of Aminophylline Infusions in Critically Ill Patients

1983 ◽  
Vol 11 (3) ◽  
pp. 220-227 ◽  
Author(s):  
K. F. Ilett ◽  
R. L. Nation ◽  
B. Silbert ◽  
T. E. Oh
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Sampling Time ◽  
Infusion Therapy ◽  
Plasma Theophylline ◽  
Total Body ◽  
Theophylline Kinetics ◽  
Body Clearance

The method of Chiou et al.4 was used to predict theophylline kinetics in eleven critically ill patients with either acute severe asthma or bronchoconstriction. Following the commencement of an accurately metered infusion of aminophylline, venous blood samples were taken at approximately 1, 5 hours and 7-12 hours for measurement of plasma theophylline concentration. The 1- and 5-hour levels were used to estimate total body clearance and plasma concentration of theophylline at the 7-12-hour sampling time. Using these values, the infusion rate was adjusted if necessary and the protocol repeated. Initial predictions were unreliable in two patients because of continued absorption of theophylline from pre-infusion therapy with aminophylline suppositories or slow-release theophylline tablets. In the remaining studies there was a significant correlation (y = 0.9x + 0.55, r2 = 0.93, p < 0.01, n = 19) between predicted and actual plasma concentrations at the 7-12-hour sampling time. In three patients, sequential estimates of theophylline clearance showed an approximate twofold variation and in another two patients, there was evidence of concentration-and/or time-dependent theophylline kinetics.

scholarly journals Copeptin and Arginine Vasopressin Concentrations in Critically Ill Patients

2006 ◽  
Vol 91 (11) ◽  
pp. 4381-4386 ◽  
Author(s):  
Stefan Jochberger ◽  
Nils G. Morgenthaler ◽  
Viktoria D. Mayr ◽  
Günter Luckner ◽  
Volker Wenzel ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Healthy Volunteers ◽  
Critically Ill ◽  
Arginine Vasopressin ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
University Teaching ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Icu Patients

Abstract Context: Determination of arginine vasopressin (AVP) concentrations may be helpful to guide therapy in critically ill patients. A new assay analyzing copeptin, a stable peptide derived from the AVP precursor, has been introduced. Objective: Our objective was to determine plasma copeptin concentrations. Design: We conducted a post hoc analysis of plasma samples and data from a prospective study. Setting: The setting was a 12-bed general and surgical intensive care unit (ICU) in a tertiary university teaching hospital. Patients: Our subjects were 70 healthy volunteers and 157 ICU patients with sepsis, with systemic inflammatory response syndrome (SIRS), and after cardiac surgery. Interventions: There were no interventions. Main Outcome Measures: Copeptin plasma concentrations, demographic data, AVP plasma concentrations, and a multiple organ dysfunction syndrome score were documented 24 h after ICU admission. Results: AVP (P &lt; 0.001) and copeptin (P &lt; 0.001) concentrations were significantly higher in ICU patients than in controls. Patients after cardiac surgery had higher AVP (P = 0.003) and copeptin (P = 0.003) concentrations than patients with sepsis or SIRS. Independent of critical illness, copeptin and AVP correlated highly significantly with each other. Critically ill patients with sepsis and SIRS exhibited a significantly higher ratio of copeptin/AVP plasma concentrations than patients after cardiac surgery (P = 0.012). The American Society of Anesthesiologists’ classification (P = 0.046) and C-reactive protein concentrations (P = 0.006) were significantly correlated with the copeptin/AVP ratio. Conclusions: Plasma concentrations of copeptin and AVP in healthy volunteers and critically ill patients correlate significantly with each other. The ratio of copeptin/AVP plasma concentrations is increased in patients with sepsis and SIRS, suggesting that copeptin may overestimate AVP plasma concentrations in these patients.

scholarly journals New Colistin Population Pharmacokinetic Data in Critically Ill Patients Suggesting an Alternative Loading Dose Rationale

2014 ◽  
Vol 58 (12) ◽  
pp. 7324-7330 ◽  
Author(s):  
N. Grégoire ◽  
O. Mimoz ◽  
B. Mégarbane ◽  
E. Comets ◽  
D. Chatelier ◽  
...  
Keyword(s):  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Loading Dose ◽  
Liquid Chromatography Tandem Mass

ABSTRACTColistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. Seventy-three critically ill patients not undergoing dialysis received multiple doses of CMS. The CMS concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and a pharmacokinetic analysis was conducted using a population approach. We confirmed that CMS renal clearance and colistin concentrations at steady state are mostly governed by creatinine clearance, but we predict a typical maximum concentration of drug in serum (Cmax) of colistin close to 2 mg/liter, occurring 3 h after an initial dose of 2 million international units (MIU) of CMS. Accordingly, the estimated colistin half-life (t1/2) was relatively short (3.1 h), with rapid attainment of steady state. Our results are only partially consistent with other recently published results. We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.

scholarly journals Population Pharmacokinetics of Unbound Ceftolozane and Tazobactam in Critically Ill Patients without Renal Dysfunction

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Fekade B. Sime ◽  
Melissa Lassig-Smith ◽  
Therese Starr ◽  
Janine Stuart ◽  
Saurabh Pandey ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Rate Constant ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Peripheral Compartment ◽  
Parameter Estimates ◽  
Pharmacokinetic Data ◽  
Dosing Regimens

ABSTRACT Evaluation of dosing regimens for critically ill patients requires pharmacokinetic data in this population. This prospective observational study aimed to describe the population pharmacokinetics of unbound ceftolozane and tazobactam in critically ill patients without renal impairment and to assess the adequacy of recommended dosing regimens for treatment of systemic infections. Patients received 1.5 or 3.0 g ceftolozane-tazobactam according to clinician recommendation. Unbound ceftolozane and tazobactam plasma concentrations were assayed, and data were analyzed with Pmetrics with subsequent Monte Carlo simulations. A two-compartment model adequately described the data from twelve patients. Urinary creatinine clearance (CLCR) and body weight described between-patient variability in clearance and central volume of distribution (V), respectively. Mean ± standard deviation (SD) parameter estimates for unbound ceftolozane and tazobactam, respectively, were CL of 7.2 ± 3.2 and 25.4 ± 9.4 liters/h, V of 20.4 ± 3.7 and 32.4 ± 10 liters, rate constant for distribution of unbound ceftolozane or tazobactam from central to peripheral compartment (Kcp) of 0.46 ± 0.74 and 2.96 ± 8.6 h−1, and rate constant for distribution of unbound ceftolozane or tazobactam from peripheral to central compartment (Kpc) of 0.39 ± 0.37 and 26.5 ± 8.4 h−1. With dosing at 1.5 g and 3.0 g every 8 h (q8h), the fractional target attainment (FTA) against Pseudomonas aeruginosa was ≥85% for directed therapy (MIC ≤ 4 mg/liter). However, for empirical coverage (MIC up to 64 mg/liter), the FTA was 84% with the 1.5-g q8h regimen when creatinine clearance is 180 ml/min/1.73 m2, whereas the 3.0-g q8h regimen consistently achieved an FTA of ≥85%. For a target of 40% of time the free drug concentration is above the MIC (40% fT>MIC), 3g q8h by intermittent infusion is suggested unless a highly susceptible pathogen is present, in which case 1.5-g dosing could be used. If a higher target of 100% fT>MIC is required, a 1.5-g loading dose plus a 4.5-g continuous infusion may be adequate.

scholarly journals Association of Serum Albumin Concentration and Mortality Risk in Critically Ill Patients

2002 ◽  
Vol 30 (2) ◽  
pp. 202-207 ◽  
Author(s):  
F. H. Y. Yap ◽  
G. M. Joynt ◽  
T. A. Buckley ◽  
E. L. Y. Wong
Keyword(s):  
Serum Albumin ◽  
Critically Ill ◽  
Mortality Risk ◽  
Critically Ill Patients ◽  
Roc Curves ◽  
Apache Ii ◽  
Surgical Patients ◽  
Apache Ii Score ◽  
Albumin Concentration ◽  
Serum Albumin Concentration

In this study we aimed to examine the association between serum albumin concentration and mortality risk in critically ill patients. We retrospectively studied 1003 patients admitted to our Intensive Care Unit (ICU) over an 18-month period. Serial albumin measurements over 72 hours were compared between survivors and non-survivors, and medical and surgical patients were also compared. Our results showed that serum albumin decreased after ICU admission, most rapidly in the first 24 hours, in both survivors and non-survivors. Serum albumin was lower in non-survivors than in survivors, but albumin concentrations poorly differentiated the two groups. Medical patients had higher admission albumin levels than surgical patients, but both subgroups showed a similar albumin profile over 72 hours. We evaluated the prognostic value of serum albumin using receiver operator characteristic (ROC) curves. We constructed ROC curves for APACHE II score, admission albumin, albumin at 24 and 48 hours. We also combined APACHE II with albumin values and constructed the corresponding ROC curves. Our data showed that serum albumin had low sensitivity and specificity for predicting hospital mortality. Combining APACHE II score with serum albumin concentrations did not improve the accuracy of outcome prediction over that of APACHE II alone.

scholarly journals Hyperosmolar Treatment for Patients at Risk for Increased Intracranial Pressure: A Single-Center Cohort Study

2020 ◽  
Vol 17 (12) ◽  
pp. 4573
Author(s):  
Agnieszka Wiórek ◽  
Tomasz Jaworski ◽  
Łukasz J. Krzych
Keyword(s):  
At Risk ◽  
Cohort Study ◽  
Intracranial Pressure ◽  
Critically Ill ◽  
Hypertonic Saline ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Plasma Sodium ◽  
Electrolyte Balance ◽  
Water And Electrolyte Balance

Treatment with osmoactive agents such as mannitol or hypertonic saline (HTS) solutions is widely used to manage or prevent the increase of intracranial pressure (ICP) in central nervous system (CNS) disorders. We sought to evaluate the variability and mean plasma concentrations of the water and electrolyte balance parameters in critically ill patients treated with osmotic therapy and their influence on mortality. This cohort study covered patients hospitalized in an intensive care unit (ICU) from January 2017 to June 2019 with presumed increased ICP or considered to be at risk of it, treated with 15% mannitol (G1, n = 27), a combination of 15% mannitol and 10% hypertonic saline (HTS) (G2, n = 33) or 10% HTS only (G3, n = 13). Coefficients of variation (Cv) and arithmetic means (mean) were calculated for the parameters reflecting the water and electrolyte balance, i.e., sodium (NaCv/NaMean), chloride (ClCv/ClMean) and osmolality (mOsmCv/mOsmMean). In-hospital mortality was also analyzed. The study group comprised 73 individuals (36 men, 49%). Mortality was 67% (n = 49). Median NaCv (G1: p = 0.002, G3: p = 0.03), ClCv (G1: p = 0.02, G3: p = 0.04) and mOsmCv (G1: p = 0.001, G3: p = 0.02) were higher in deceased patients. NaMean (p = 0.004), ClMean (p = 0.04), mOsmMean (p = 0.003) were higher in deceased patients in G3. In G1: NaCv (AUC = 0.929, p < 0.0001), ClCv (AUC = 0.817, p = 0.0005), mOsmCv (AUC = 0.937, p < 0.0001) and in G3: NaMean (AUC = 0.976, p < 0.001), mOsmCv (AUC = 0.881, p = 0.002), mOsmMean (AUC = 1.00, p < 0.001) were the best predictors of mortality. The overall mortality prediction for combined G1+G2+G3 was very good, with AUC = 0.886 (p = 0.0002). The mortality of critically ill patients treated with osmotic agents is high. Electrolyte disequilibrium is the independent predictor of mortality regardless of the treatment method used. Variations of plasma sodium, chloride and osmolality are the most deleterious factors regardless of the absolute values of these parameters

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