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.

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.

A new method for the estimation of the components of energy expenditure in patients with major trauma

1994 ◽  
Vol 267 (6) ◽  
pp. E1002-E1009 ◽  
Author(s):  
G. Franch-Arcas ◽  
L. D. Plank ◽  
D. N. Monk ◽  
R. Gupta ◽  
K. Maher ◽  
...  
Keyword(s):  
Body Composition ◽  
Energy Expenditure ◽  
Critically Ill ◽  
Indirect Calorimetry ◽  
Critically Ill Patients ◽  
Major Trauma ◽  
Calorie Intake ◽  
Total Body Potassium ◽  
Body Protein ◽  
Total Body

The management of critically ill patients would be better understood if the total energy expenditure (TEE) and its components are known. To quantify the different components of energy expenditure in patients with major trauma, we used a technique combining measurements of body composition and oxygen consumption. We determined changes in body weight, total body water, total body protein, total body potassium, total body fat, and bone mineral content every 5 days over a 10-day period in a group of nine multiply injured patients. Resting energy expenditure was measured by indirect calorimetry (REEm), and a predicted value was obtained from total body potassium (REEp). TEE was assessed by adding the total calorie intake to the changes in body energy stores, and the activity energy expenditure (AEE) was calculated by subtracting REEm from TEE. Mean daily values for REEm, REEp, TEE, and AEE were 2,236 +/- 140, 1,683 +/- 82, 3,029 +/- 276, and 793 +/- 213 kcal/day, respectively, over the 10-day study period. Although not statistically significant, the mean AEE was four times smaller for the first 5 days of study than for the second 5 days (298 +/- 400 vs. 1,254 +/- 588 kcal/day). The technique of combining indirect calorimetry and body composition measurements offers a new approach to evaluate energy expenditure and a new way to study metabolic disorders and therapeutic strategies in critically ill patients.

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 Anidulafungin in Critically Ill Patients

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
S. Luque ◽  
W. Hope ◽  
N. Campillo ◽  
R. Muñoz-Bermúdez ◽  
L. Sorli ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Model ◽  
Candida Glabrata ◽  
Total Body Weight ◽  
Content Type ◽  
Final Population ◽  
Dosage Escalation ◽  
Optimal Drug ◽  
Total Body

ABSTRACT A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

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