scholarly journals Serum and peritoneal exudate concentrations after high doses of β-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study

2019 ◽  
Vol 75 (1) ◽  
pp. 156-161
Author(s):  
Lisa Leon ◽  
Philippe Guerci ◽  
Elise Pape ◽  
Nathalie Thilly ◽  
Amandine Luc ◽  
...  
Keyword(s):  
Steady State ◽  
Prospective Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
A Priori ◽  
Peritoneal Exudate ◽  
Observational Prospective Study ◽  
Lactam Antibiotic ◽  
High Doses ◽  
Abdominal Infections

Abstract Background Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to β-lactam underdosage. Objectives To measure serum and peritoneal exudate concentrations of β-lactams after high doses and optimal administration schemes. Methods This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a β-lactam antibiotic as empirical therapy. Serum and peritoneal exudate concentrations were measured during surgery and after a 24 h steady-state period. The PK/pharmacodynamic (PD) target was to obtain serum β-lactam concentrations of 100% fT>4×MIC based on a worst-case scenario (based on the EUCAST highest epidemiological cut-off values) before bacterial documentation (a priori) and redefined following determination of the MIC for the isolated bacteria (a posteriori). Registered with ClinicalTrials.gov (NCT03310606). Results Forty-eight patients were included with a median (IQR) age of 64 (53–74) years and a SAPS II of 40 (32–65). The main diagnosis was secondary nosocomial peritonitis. Piperacillin/tazobactam was the most administered β-lactam antibiotic (75%). The serum/peritoneal piperacillin/tazobactam ratio was 0.88 (0.64–0.97) after a 24 h steady-state period. Prior to bacterial documentation, 16 patients (33.3%) achieved the a priori PK/PD target. The identification of microorganisms was available for 34 patients (71%). Based on the MIC for isolated bacteria, 78% of the patients achieved the serum PK/PD target. Conclusions In severe IAIs, high doses of β-lactams ensured 100% fT>4×MIC in the serum for 78% of critically ill patients with severe IAIs within the first 24 h. In order to define optimal β-lactam dosing, the PK/PD target should take into account the tissue penetration and local ecology.

Comparison of the renal effects of low to high doses of dopamine and dobutamine in critically ill patients: A single-blind randomized study

2000 ◽  
Vol 28 (4) ◽  
pp. 921-928 ◽  
Author(s):  
Carole Ichai ◽  
Jérôme Soubielle ◽  
M. Carles ◽  
Carine Giunti ◽  
Dominique Grimaud
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Randomized Study ◽  
Renal Effects ◽  
High Doses ◽  
Single Blind

scholarly journals Pharmacokinetics of Amphotericin B Colloidal Dispersion in Critically Ill Patients with Cholestatic Liver Disease

2012 ◽  
Vol 56 (10) ◽  
pp. 5414-5418 ◽  
Author(s):  
Stefan Weiler ◽  
Elisabeth Überlacher ◽  
Julia Schöfmann ◽  
Eva Stienecke ◽  
Stefan Dunzendorfer ◽  
...  
Keyword(s):  
Steady State ◽  
Liver Disease ◽  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Liver ◽  
Colloidal Dispersion ◽  
Cholestatic Liver Disease ◽  
Normal Liver Function ◽  
Standard Dosage

ABSTRACTThe pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.

scholarly journals Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria

2009 ◽  
Vol 53 (8) ◽  
pp. 3430-3436 ◽  
Author(s):  
D. Plachouras ◽  
M. Karvanen ◽  
L. E. Friberg ◽  
E. Papadomichelakis ◽  
A. Antoniadou ◽  
...  
Keyword(s):  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Colistin Methanesulfonate

ABSTRACT Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

Continuous infusion versus intermittent administration of ceftazidime in critically ill patients with suspected gram-negative infections.

1996 ◽  
Vol 40 (3) ◽  
pp. 691-695 ◽  
Author(s):  
A S Benko ◽  
D M Cappelletty ◽  
J A Kruse ◽  
M J Rybak
Keyword(s):  
Steady State ◽  
Continuous Infusion ◽  
Clinical Isolate ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Apache Ii Score ◽  
Serum Drug Concentration ◽  
Gram Negative ◽  
Intermittent Bolus ◽  
Standard Deviations

The pharmacodynamics and pharmacokinetics of ceftazidime administered by continuous infusion and intermittent bolus over a 4-day period were compared. We conducted a prospective, randomized, crossover study of 12 critically ill patients with suspected gram-negative infections. The patients were randomized to receive ceftazidime either as a 2-g intravenous (i.v.) loading dose followed by a 3-g continuous infusion (CI) over 24 h or as 2 g i.v. every 8 h (q8h), each for 2 days. After 2 days, the patients were crossed over and received the opposite regimen. Each regimen also included tobramycin (4 to 7 mg/kg of body weight, given i.v. q24h). Eighteen blood samples were drawn on study days 2 and 4 to evaluate the pharmacokinetics of ceftazidime and its pharmacodynamics against a clinical isolate of Pseudomonas aeruginosa (R288). The patient demographics (means +/- standard deviations) were as follows: age, 57 +/- 12 years; sex, nine males and three females; APACHE II score, 15 +/- 3; diagnosis, 9 of 12 patients with pneumonia. The mean pharmacokinetic parameters for ceftazidime given as an intermittent bolus (IB) (means +/- standard deviations) were as follows: maximum concentration of drug in serum, 124.4 +/- 52.6 micrograms/ml; minimum concentration in serum, 25.0 +/- 17.5 micrograms/ml; elimination constant, 0.268 +/- 0.205 h-1; half-life, 3.48 +/- 1.61 h; and volume of distribution, 18.9 +/- 9.0 liters. The steady-state ceftazidime concentration for CI was 29.7 +/- 17.4 micrograms/ml, which was not significantly different from the targeted concentrations. The range of mean steady-state ceftazidime concentrations for the 12 patients was 10.6 to 62.4 micrograms/ml. Tobramycin peak concentrations ranged between 7 and 20 micrograms/ml. As expected, the area under the curve for the 2-g q8h regimen was larger than that for CI (P = 0.003). For IB and CI, the times that the serum drug concentration was greater than the MIC were 92 and 100%, respectively, for each regimen against the P. aeruginosa clinical isolate. The 24-h bactericidal titers in serum, at which the tobramycin concentrations were < 1.0 microgram/ml in all patients, were the same for CI and IB (1:4). In the presence of tobramycin, the area under the bactericidal titer-time curve (AUBC) was significantly greater for IB than CI (P = 0.001). After tobramycin was removed from the serum, no significant difference existed between the AUBCs for CI and IB. We conclude that CI of ceftazidime utilizing one-half the IB daily dose was equivalent to the IB treatment as judged by pharmacodynamic analysis of critically ill patients with suspected gram-negative infections. No evaluation comparing the clinical efficacies of these two dosage regimens was performed.

Very-low-dose ketamine for the management of pain and sedation in the ICU

2018 ◽  
Vol 4 (1) ◽  
pp. 54 ◽  
Author(s):  
Mario De Pinto, MD ◽  
Jill Jelacic, MD ◽  
William T. Edwards, PhD, MD
Keyword(s):  
Mechanical Ventilation ◽  
Case Report ◽  
Respiratory Depression ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Low Dose ◽  
Anesthetic Agent ◽  
Cardiovascular Instability ◽  
High Doses ◽  
Very High

Management of pain in critically ill patients can be very difficult. In the attempt to provide comfort with adequate levels of opioids and sedatives, respiratory depression and cardiovascular instability may become difficult to control in patients with labile hemodynamics and poor cardiopulmonary reserve. The use of medications like ketamine, an anesthetic agent that in subanesthetic doses has been reported to be effective in preventing opioidinduced tolerance and to have analgesic properties, may be of help, especially in patients who develop tolerance, leading to rapidly escalating doses of opioids and sedatives. The case report presented here shows how a very low dose of ketamine can be helpful for the management of pain and sedation in critically ill patients, especially when they are ready to be weaned from mechanical ventilation, and very high doses of opiods and sedatives do not permit it.

Dialysis and central venous catheter infections in critically ill patients: Results of a prospective study

1999 ◽  
Vol 27 (11) ◽  
pp. 2394-2398 ◽  
Author(s):  
Bertrand Souweine ◽  
Ousmane Traore ◽  
Bruno Aublet-Cuvelier ◽  
Laurence Badrikian ◽  
Laurent Bret ◽  
...  
Keyword(s):  
Central Venous Catheter ◽  
Prospective Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Venous Catheter ◽  
Central Venous ◽  
A Prospective Study ◽  
Catheter Infections

scholarly journals A prospective study of the incidence of iatrogenic ocular damage in critically ill patients

Critical Care ◽  
10.1186/cc376 ◽  
1999 ◽  
Vol 3 (Suppl 1) ◽  
pp. P001
Author(s):  
C Gorman ◽  
T Rogers ◽  
J Price ◽  
A Waboso ◽  
L Flackett ◽  
...  
Keyword(s):  
Prospective Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
A Prospective Study
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