scholarly journals Dose Optimization of Vancomycin for Critically Ill Patients Undergoing CVVH: A Prospective Population PK/PD Analysis

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1392
Author(s):  
Chuhui Wang ◽  
Chao Zhang ◽  
Xiaoxiao Li ◽  
Sixuan Zhao ◽  
Na He ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Dosage Regimen ◽  
Surgical Intensive Care Unit ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Recommended Dosage ◽  
Surgical Intensive Care ◽  
Dosage Regimens ◽  
Vancomycin Dosage

The optimal dose of vancomycin in critically ill patients receiving continuous venovenous hemofiltration (CVVH) remains unclear. The objective of this study was to identify factors that significantly affect pharmacokinetic profiles and to further investigate the optimal dosage regimens for critically ill patients undergoing CVVH based on population pharmacokinetics and pharmacodynamic analysis. A prospective population pharmacokinetic analysis was performed at the surgical intensive care unit in a level A tertiary hospital. We included 11 critically ill patients undergoing CVVH and receiving intravenous vancomycin. Serial blood samples were collected from each patient, with a total of 131 vancomycin concentrations analyzed. Nonlinear mixed effects models were developed using NONMEM software. Monte Carlo Simulation was used to optimize vancomycin dosage regimens. A two-compartment model with first-order elimination was sufficient to characterize vancomycin pharmacokinetics for CVVH patients. The population typical vancomycin clearance (CL) was 1.15 L/h and the central volume of distribution was 16.9 L. CL was significantly correlated with ultrafiltration rate (UFR) and albumin level. For patients with normal albumin and UFR between 20 and 35 mL/kg/h, the recommended dosage regimen was 10 mg/kg qd. When UFR was between 35 and 40 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. For patients with hypoalbuminemia and UFR between 20 and 25 mL/kg/h, the recommended dosage regimen was 5 mg/kg q8h. When UFR was between 25 and 40 mL/kg/h, the recommended dosage regimen was 10 mg/kg q12h. We recommend clinicians choosing the optimal initial vancomycin dosage regimens for critically ill patients undergoing CVVH based on these two covariates.

A Double-blind, Randomized Comparison of IV Lorazepam versus  Midazolam for Sedation of ICU Patients via  a Pharmacologic Model

2001 ◽  
Vol 95 (2) ◽  
pp. 286-298 ◽  
Author(s):  
Juliana Barr ◽  
Katayoun Zomorodi ◽  
Edward J. Bertaccini ◽  
Steven L. Shafer ◽  
Eran Geller
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Sedation Score ◽  
Surgical Intensive Care Unit ◽  
Population Pharmacokinetic ◽  
Surgical Intensive Care ◽  
Double Blind ◽  
Icu Patients ◽  
Intravenous Infusions

Background Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients. Methods With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling. Results A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or = ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. Conclusions The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.

Implementing Volume-Based Feeding to Optimize Delivery of Enteral Nutrition

2021 ◽  
Vol 41 (2) ◽  
pp. 16-26
Author(s):  
Angela Bonomo ◽  
Diane Lynn Blume ◽  
Katie Davis ◽  
Hee Jun Kim
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Quality Improvement ◽  
Enteral Nutrition ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Educational Approach ◽  
Lecture Demonstration

Background At least 80% of ordered enteral nutrition should be delivered to improve outcomes in critical care patients. However, these patients typically receive 60% to 70% of ordered enteral nutrition volume. In a practice review within a 28-bed medical-surgical adult intensive care unit, patients received a median of 67.5% of ordered enteral nutrition with standard rate-based feeding. Volume-based feeding is recommended to deliver adequate enteral nutrition to critically ill patients. Objective To use a quality improvement project to increase the volume of enteral nutrition delivered in the medical-surgical intensive care unit. Methods Percentages of target volume achieved were monitored in 73 patients. Comparisons between the rate-based and volume-based feeding groups used nonparametric quality of medians test or the χ2 test. A customized volume-based feeding protocol and order set were created according to published protocols and then implemented. Standardized education included lecture, demonstration, written material, and active personal involvement, followed by a scenario-based test to apply learning. Results Immediately after implementation of this practice change, delivered enteral nutrition volume increased, resulting in a median delivery of 99.8% of ordered volume (P = .003). Delivery of a mean of 98% ordered volume was sustained over the 15 months following implementation. Conclusions Implementation of volume-based feeding optimized enteral nutrition delivery to critically ill patients in this medical-surgical intensive care unit. This success can be attributed to a comprehensive, individualized, and proactive process design and educational approach. The process can be adapted to quality improvement initiatives with other patient populations and units.

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.

Prognosis of Critically Ill Patients With Cancer and Acute Renal Dysfunction

2006 ◽  
Vol 24 (24) ◽  
pp. 4003-4010 ◽  
Author(s):  
Márcio Soares ◽  
Jorge I.F. Salluh ◽  
Marilia S. Carvalho ◽  
Michael Darmon ◽  
José R. Rocco ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Model ◽  
Mortality Rates ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Acute Renal Dysfunction ◽  
Patients With Cancer ◽  
Organ Failures

Purpose To evaluate the outcomes of critically ill patients with cancer and acute renal dysfunction. Patients and Methods Prospective cohort study conducted at a 10-bed oncologic medical-surgical intensive care unit (ICU) over a 56-month period. Results Of 975 patients, 309 (32%) had renal dysfunction and were studied. Their mean age was 60.9 ± 15.9 years; 233 patients (75%) had solid tumors and 76 (25%) had hematologic malignancies. During the ICU stay, 98 patients (32%) received dialysis. Renal dysfunction was multifactorial in 56% of the patients, and the main associated factors were shock/ischemia (72%) and sepsis (63%). Overall hospital and 6-month mortality rates were 64% and 73%, respectively. Among patients who required dialysis, mortality rates were lower in patients who received dialysis on the first day of ICU in comparison with those who required it thereafter. In a multivariable Cox model, age more than 60 years, uncontrolled cancer, impaired performance status, and more than two associated organ failures were associated with increased 6-month mortality. Renal function was completely re-established in 82% and partially re-established in 12%, and only 6% of survivors required chronic dialysis. Conclusion Acute renal dysfunction is frequent in critically ill patients with cancer. Although mortality rates are high, selected patients can benefit from ICU care and advanced organ support. When evaluating prognosis and the appropriateness of dialysis in these patients, older age, functional capacity, cancer status and the severity of associated organ failures are important variables to take into consideration.

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 < 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.

scholarly journals Effect of Persistent Thrombocytopenia on Mortality in Surgical Critical Care Patients

2016 ◽  
Vol 23 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Qin Wu ◽  
Jianan Ren ◽  
Gefei Wang ◽  
Guanwei Li ◽  
Nadeem Anjum ◽  
...  
Keyword(s):  
Critical Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Surgical Critical Care ◽  
Hospital Stays ◽  
Clinically Significant ◽  
The Relationship ◽  
Persistent Thrombocytopenia

Thrombocytopenia is common among surgical critically ill patients. The relationship between the duration of thrombocytopenia and mortality is not well studied. This retrospective 12-month cohort study was designed to evaluate the association between persistent thrombocytopenia and mortality among surgical critically ill patients to determine the risk factors for persistent thrombocytopenia. The study included adult patients consecutively admitted to the surgical intensive care unit (SICU) at our institution. Patients with a diagnosis of thrombocytopenia were identified from a prospective critical care database. We defined patients with persistent thrombocytopenia as those with thrombocytopenia lasting more than 7 consecutive days. The primary outcome of this study was 28-day mortality and the secondary outcomes were lengths of SICU stay and hospital stay. Fifty-one patients experienced persistent thrombocytopenia and 71 experienced nonpersistent thrombocytopenia. Among patients with persistent thrombocytopenia, mortality was significantly higher, and SICU and hospital stays were longer than those with nonpersistent thrombocytopenia. Risk factor analysis failed to predict which patients with thrombocytopenia would develop into persistent thrombocytopenia. Persistent thrombocytopenia is a clinically significant disorder and is associated with poorer outcomes. Future studies are needed to further define this process.

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 Measurement of the nociceptive flexion reflex threshold in critically ill patients – a randomized observational pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Benedikt Schick ◽  
Benjamin Mayer ◽  
Steffen Walter ◽  
Sascha Gruss ◽  
Ronald Stitz ◽  
...  
Keyword(s):  
Pilot Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
University Hospital ◽  
Surgical Intensive Care Unit ◽  
Surgical Intensive Care ◽  
Mechanically Ventilated ◽  
Flexion Reflex ◽  
Nociceptive Flexion Reflex ◽  
Reflex Threshold

Abstract Background Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. Methods This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). Results 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 – NFRT: 59.40 vs. RASS -4 – NFRT: 29.00, p < 0.001). Conclusions NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ −4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. Trial Registration Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149.

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