Assessment of Interindividual Variability of Plasma Concentrations after Administration of High Doses of Intravenous Amoxicillin or Cloxacillin in Critically Ill Patients

Abstract Objectives To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Patients and methods Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded. Results Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12–0.33), 0.20 (0.11–0.24), 0.17 (0.12–0.23) and 0.17 (0.11–0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11–0.35), 0.24 (0.12–0.44), 0.24 (0.10–0.49) and 0.23 (0.11–0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed. Conclusions In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

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

Critical Care Medicine ◽

10.1097/00003246-200004000-00002 ◽

2000 ◽

Vol 28 (4) ◽

pp. 921-928 ◽

Cited By ~ 37

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

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

Medical academic journal ◽

10.17816/maj54636 ◽

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.

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

10.21203/rs.3.rs-43580/v1 ◽

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.

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Pharmacokinetic Optimisation of Aminophylline Infusions in Critically Ill Patients

Anaesthesia and Intensive Care ◽

10.1177/0310057x8301100307 ◽

1983 ◽

Vol 11 (3) ◽

pp. 220-227 ◽

Cited By ~ 1

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.

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

Journal of Opioid Management ◽

10.5055/jom.2008.0009 ◽

2018 ◽

Vol 4 (1) ◽

pp. 54 ◽

Cited By ~ 20

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.

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Copeptin and Arginine Vasopressin Concentrations in Critically Ill Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-2830 ◽

2006 ◽

Vol 91 (11) ◽

pp. 4381-4386 ◽

Cited By ~ 90

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 < 0.001) and copeptin (P < 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.

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Intravenous Therapy with High Doses of Ranitidine and Omeprazole in Critically Ill Patients with Bleeding Peptic Ulcerations of the Upper Intestinal Tract: An Open Randomized Controlled Trial

Digestion ◽

10.1159/000200249 ◽

1990 ◽

Vol 45 (4) ◽

pp. 217-225 ◽

Cited By ~ 62

Author(s):

G. Brunner ◽

J. Chang

Keyword(s):

Randomized Controlled Trial ◽

Critically Ill ◽

Critically Ill Patients ◽

Intestinal Tract ◽

Controlled Trial ◽

Intravenous Therapy ◽

Randomized Controlled ◽

High Doses

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03508-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7324-7330 ◽

Cited By ~ 50

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.

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