scholarly journals Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

2019 ◽  
Vol 7 (4) ◽  
pp. 155-169
Author(s):  
Dominique Breilh ◽  
Patrick M. Honore ◽  
David De Bels ◽  
Jason A. Roberts ◽  
Jean Baptiste Gordien ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Half Life ◽  
Antimicrobial Agents ◽  
High Volume ◽  
Lessons Learned ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Dose Recommendations ◽  
Spearman Test

Abstract Background Hemofiltration rate, changes in blood and ultrafiltration flow, and discrepancies between the prescribed and administered doses strongly influence pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents during continuous veno-venous hemofiltration (CVVH) in critically ill patients. Methods Ancillary data were from the prospective multicenter IVOIRE (hIgh VOlume in Intensive caRE) study. High volume (HV, 70 mL/kg/h) was at random compared with standard volume (SV, 35 mL/kg/h) CVVH in septic shock patients with acute kidney injury (AKI). PK/PD parameters for all antimicrobial agents used in each patient were studied during five days. Results Antimicrobial treatment met efficacy targets for both percentage of time above the minimal inhibitory concentration and inhibitory quotient. A significant correlation was observed between the ultrafiltration flow and total systemic clearance (Spearman test: P < 0.005) and between CVVH clearance and drug elimination half-life (Spearman test: P < 0.005). All agents were easily filtered. Mean sieving coefficient ranged from 38.7% to 96.7%. Mean elimination half-life of all agents was significantly shorter during HV-CVVH (from 1.29 to 28.54 h) than during SV-CVVH (from 1.51 to 33.85 h) (P < 0.05). Conclusions This study confirms that CVVH influences the PK/PD behavior of most antimicrobial agents. Antimicrobial elimination was directly correlated with convection rate. Current antimicrobial dose recommendations will expose patients to underdosing and increase the risk for treatment failure and development of resistance. Dose recommendations are proposed for some major antibiotic and antifungal treatments in patients receiving at least 25 mL/kg/h CVVH.

scholarly journals Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration

2010 ◽  
Vol 54 (7) ◽  
pp. 2974-2978 ◽  
Author(s):  
I. Bilgrami ◽  
J. A. Roberts ◽  
S. C. Wallis ◽  
J. Thomas ◽  
J. Davis ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
High Volume ◽  
Volume Of Distribution ◽  
Continuous Venovenous Hemofiltration ◽  
Drug Dosing ◽  
Elimination Half ◽  
Lower Volume ◽  
Dosing Regimens ◽  
Few Data

ABSTRACT Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. The objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume CVVHF with high-volume exchanges (≥4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] every 8 h) are sufficient for treatment of less susceptible organisms such as Burkholderia pseudomallei (MIC, 4 mg/liter); and, finally, to compare the clearances observed in this study with data from previous studies using lower-volume exchanges (1 to 2 liters/h). We recruited 10 eligible patients and collected serial pre- and postfilter blood samples and ultrafiltrate and urine samples. A noncompartmental method was used to determine meropenem pharmacokinetics. The cohort had a median age of 56.6 years, a median weight of 70 kg, and a median APACHE II (acute physiology and chronic health evaluation) score of 25. The median (interquartile range) values for meropenem were as follows: terminal elimination half-life, 4.3 h (2.9 to 6.0); terminal volume of distribution, 0.2 liters/kg (0.2 to 0.3); trough concentration, 7.7 mg/liter (6.2 to 12.9); total clearance, 6.0 liters/h (5.2 to 6.2); hemofiltration clearance, 3.5 liters/h (3.4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (R 2 = 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as B. pseudomallei.

scholarly journals Altered Pharmacokinetics of Ceftazidime in Critically Ill Patients

1999 ◽  
Vol 43 (7) ◽  
pp. 1798-1802 ◽  
Author(s):  
C. M. H. Gómez ◽  
J. J. Cordingly ◽  
M. G. A. Palazzo
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Half Life ◽  
Extracellular Fluid ◽  
Area Under The Curve ◽  
Drug Distribution ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Terminal Phase ◽  
Elimination Half

ABSTRACT Many critically ill patients have increased extracellular fluid which might affect ceftazidime pharmacokinetics. We investigated the pharmacokinetics of ceftazidime in 15 adult intensive care patients receiving 2 g of ceftazidime intravenously three times a day. The ceftazidime mean (standard deviation) apparent volume of distribution and terminal-phase half-life were 56.91 (25.93) liters and 4.75 (1.85) h, respectively, significantly greater than values reported previously for healthy controls (P < 0.001). The mean ceftazidime clearance and area under the curve at steady state were not significantly different from those previously reported for controls. We conclude that ceftazidime pharmacokinetics in critically ill patients were altered by an increased volume of drug distribution and elevated elimination half-life.

Influence of concomitant drugs on methadone elimination half-life in patients under a maintenance treatment

2001 ◽  
Vol 6 (2) ◽  
pp. 171-176 ◽  
Author(s):  
A. C. S. Lucas ◽  
A. M. Bermejo ◽  
M. J. Tabernero ◽  
P. FernÁNdez ◽  
P. CÁMpora
Keyword(s):  
Half Life ◽  
Maintenance Treatment ◽  
Elimination Half Life ◽  
Elimination Half

Lactic Acidosis, Hyperglycaemia and Convulsions following Nalidixic Acid Overdosage

1984 ◽  
Vol 3 (3) ◽  
pp. 239-243 ◽  
Author(s):  
P.J.A. Leslie ◽  
R.J. Cregeen ◽  
A.T. Proudfoot
Keyword(s):  
Plasma Concentration ◽  
Lactic Acidosis ◽  
Nalidixic Acid ◽  
Half Life ◽  
Abnormal Behaviour ◽  
Elimination Half Life ◽  
Elimination Half

1 A woman survived ingestion of 32 g nalidixic acid despite developing lactic acidosis, hyperglycaemia, convulsions and abnormal behaviour. 2 The maximum recorded plasma concentration of nalidixic acid was 185 mg/l and the elimination half-life was 3.2 h. 3 Carboxy-nalidixic acid was demonstrated in the plasma. 4 Previously reported cases of nalidixic acid overdosage are reviewed.

Elimination Half-Life

2010 ◽  
pp. 475-475
Author(s):  
Bart Ellenbroek ◽  
Alfonso Abizaid ◽  
Shimon Amir ◽  
Martina de Zwaan ◽  
Sarah Parylak ◽  
...  
Keyword(s):  
Half Life ◽  
Elimination Half Life ◽  
Elimination Half

Candidiasis

2018 ◽  
Author(s):  
Brett A Melnikoff ◽  
René P Myers
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Diagnostic Methods ◽  
Ventricular Assist Devices ◽  
Transplant Recipients ◽  
Ventricular Assist ◽  
Disseminated Candidiasis ◽  
Candida Infections

Fungal infections remain an important cause of morbidity and mortality in surgical settings, with critically ill patients, transplant recipients, and sick neonates all especially vulnerable. Over the past few decades, technological and scientific advancements have improved physicians’ ability to sustain life in critically ill patients; developments in chemotherapeutics and immune-based therapies have yielded increased survival for many cancer patients; organ transplantation has evolved dramatically; and the use of invasive therapies (eg, ventricular assist devices) has increased markedly. With these changes has come an increase in the incidence of serious Candida infections. This review covers the definition and classification, epidemiology and risk factors, and clinical evaluation of candidiasis, as well as management of candidemia, acute disseminated candidiasis, nonhematogenous candidiasis, and peritonitis and intra-abdominal abscess. Figures show Candida endophthalmitis in patients with persistent fungemia and superficial candidiasis in the gastrointestinal tract. Tables list clinical presentation and diagnostic methods for common fungal infections, antimicrobial agents of choice for candidal infections, and the latest guidelines for candidiasis. This review contains 2 figures, 3 tables and 131 references Key words: acute disseminated candidiasis, candidemia, candidiasis, candiduria, nonhematogenous candidiasis  

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