scholarly journals Low Caspofungin Exposure in Patients in Intensive Care Units

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Kim C. M. van der Elst ◽  
Anette Veringa ◽  
Jan G. Zijlstra ◽  
Albertus Beishuizen ◽  
Rob Klont ◽  
...  
Keyword(s):  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Standard Dose ◽  
Drug Distribution ◽  
Volume Of Distribution ◽  
Primary Objective ◽  
Time Curve ◽  
Icu Patients

ABSTRACT In critically ill patients, drug exposure may be influenced by altered drug distribution and clearance. Earlier studies showed that the variability in caspofungin exposure was high in intensive care unit (ICU) patients. The primary objective of this study was to determine if the standard dose of caspofungin resulted in adequate exposure in critically ill patients. A multicenter prospective study in ICU patients with (suspected) invasive candidiasis was conducted in the Netherlands from November 2013 to October 2015. Patients received standard caspofungin treatment, and the exposure was determined on day 3 of treatment. An area under the concentration-time curve from 0 to 24 h (AUC0–24) of 98 mg · h/liter was considered adequate exposure. In case of low exposure (i.e., <79 mg · h/liter, a ≥20% lower AUC0–24), the caspofungin dose was increased and the exposure reevaluated. Twenty patients were included in the study, of whom 5 had a positive blood culture. The median caspofungin AUC0–24 at day 3 was 78 mg · h/liter (interquartile range [IQR], 69 to 97 mg · h/liter). A low AUC0–24 (<79 mg · h/liter) was seen in 10 patients. The AUC0–24 was significantly and positively correlated with the caspofungin dose in mg/kg/day (P = 0.011). The median AUC0–24 with a caspofungin dose of 1 mg/kg was estimated using a pharmacokinetic model and was 114.9 mg · h/liter (IQR, 103.2 to 143.5 mg · h/liter). In conclusion, the caspofungin exposure in ICU patients in this study was low compared with that in healthy volunteers and other (non)critically ill patients, most likely due to a larger volume of distribution. A weight-based dose regimen is probably more suitable for patients with substantially altered drug distribution. (This study has been registered at ClinicalTrials.gov under registration no. NCT01994096.)

scholarly journals Pharmacokinetics of Anidulafungin in Critically Ill Intensive Care Unit Patients with Suspected or Proven Invasive Fungal Infections

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
R. J. M. Brüggemann ◽  
V. Middel-Baars ◽  
D. W. de Lange ◽  
A. Colbers ◽  
A. R. J. Girbes ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill ◽  
Fungal Infections ◽  
Geometric Mean ◽  
Volume Of Distribution ◽  
Time Curve ◽  
Icu Patients ◽  
Minimum Concentration ◽  
Median Volume

ABSTRACT Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0–24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg · h · liter−1, a median daily trough concentration (C 24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (C max) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters · h−1. Pharmacokinetic sampling on day 7 (n = 13) resulted in a median AUC0–24 of 82.7 (IQR, 73.0 to 129.5) mg · h · liter−1, a median minimum concentration of drug in serum (C min) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median C max of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters · h−1. The geometric mean ratio for the AUCday7/AUCday3 term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.)

scholarly journals In VivoMicrodialysis To Determine Subcutaneous Interstitial Fluid Penetration and Pharmacokinetics of Fluconazole in Intensive Care Unit Patients with Sepsis

2015 ◽  
Vol 60 (2) ◽  
pp. 827-832 ◽  
Author(s):  
Mahipal G. Sinnollareddy ◽  
Michael S. Roberts ◽  
Jeffrey Lipman ◽  
Melissa Lassig-Smith ◽  
Therese Starr ◽  
...  
Keyword(s):  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
High Performance ◽  
Interstitial Fluid ◽  
Drug Exposure ◽  
Pharmacokinetic Analysis ◽  
Time Curve ◽  
Fluid Penetration

ABSTRACTThe objective of the study was to describe the subcutaneous interstitial fluid (ISF) pharmacokinetics of fluconazole in critically ill patients with sepsis. This prospective observational study was conducted at two tertiary intensive care units in Australia. Serial fluconazole concentrations were measured over 24 h in plasma and subcutaneous ISF using microdialysis. The concentrations in plasma and microdialysate were measured using a validated high-performance liquid chromatography system with electrospray mass spectrometer detector method. Noncompartmental pharmacokinetic analysis was performed. Twelve critically ill patients with sepsis were enrolled. The meanin vivofluconazole recovery rates ± standard deviation (SD) for microdialysis were 51.4% ± 16.1% with a mean (±SD) fluconazole ISF penetration ratio of 0.52 ± 0.30 (coefficient of variation, 58%). The median free plasma area under the concentration-time curve from 0 to 24 h (AUC0–24) was significantly higher than the median ISF AUC0–24(340.4 versus 141.1 mg · h/liter;P= 0.004). There was no statistical difference in median fluconazole ISF penetration between patients receiving and not receiving vasopressors (median, 0.28 versus 0.78;P= 0.106). Both minimum and the maximum concentrations of drug in serum (CmaxandCmin) showed a significant correlation with the fluconazole plasma exposure (Cmax,R2=0.86,P< 0.0001;Cmin,R2= 0.75,P< 0.001). Our data suggest that fluconazole was distributed variably, but incompletely, from plasma into subcutaneous interstitial fluid in this cohort of critically ill patients with sepsis. Given the variability of fluconazole interstitial fluid exposures and lack of clinically identifiable factors by which to recognize patients with reduced distribution/exposure, we suggest higher than standard doses to ensure that drug exposure is adequate at the site of infection.

scholarly journals Discomforts in Critically ill Patients: Our Experience in Intensive Care Unit of a Tertiary Care Hospital in India

2021 ◽  
Author(s):  
Reetu Verma ◽  
Sasmita Panda ◽  
Rajeev Kumar Nishad
Keyword(s):  
Intensive Care ◽  
Environmental Factors ◽  
Critically Ill ◽  
Nursing Care ◽  
Critically Ill Patients ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Care Hospital ◽  
Icu Patients ◽  
Common Cause

Introduction: Patients admitted in the Intensive Care Units (ICUs) experiences various discomforts which may be recognised or unrecognised. These discomforts may arise from the environment, may be related to the ICU care and discomfort related to the health status of the patient and critical care interventions. Aim: To identify the various discomforts in ICU patients, to classify them with respective causes, identify the most common cause among them and whether ICU sedation helps in reducing discomforts. Materials and Methods: This observational study was conducted from 15th July to 15th October 2018 on 120 mixed ICU patients in a Tertiary Care Hospital in India. Patients who were admitted to ICU for more than 24 hours, aged 18 years and above, those who gave written informed consent were observed and enquired for any discomfort. Discomforts have been identified and recorded by a fulltime intensivist by direct observation, by interacting with the patients and asking the family members and others (indirect approach). Through this study discomforts of critically ill patients were broadly classified into four categories 1. Due to existing illness, 2. Due to ICU interventions, 3. Due to improper nursing care and 4. Due to environmental factors. Results: Out of 120 patients studied, 84 patients (70%) reported some kind of discomfort during their ICU stay. Existing illness was the most common cause of discomfort, 80 patients (66.6%) suffered due to it. ICU interventions was the second most common cause, 71 patients (59.1%) had discomfort due to interventions. Thirty five patients (29.1%) suffered due to improper nursing care and 25 patients (20.8%) suffered due to the environmental factors. In this study, it was observed that sedation reduces all kind of discomforts. conclusion: In this study 70% of patients, who were admitted to ICU due to various illness reported some kind of discomfort. The most common cause of ICU discomforts was existing illness followed by ICU interventions. In this study it was observed that sedation reduces all kind of discomforts. Sedated patients tolerate the endotracheal tube better and they had less environmental and procedure related discomforts. With the present study observation it can be suggested that ICU charts of nurses and doctors can carry a separate column for mentioning discomforts in different duty shifts. However, with the use of appropriate analgesia and sedation discomfort can be reduced.

scholarly journals Methadone Pharmacokinetics in Geriatric Critically Ill Patients Following Intramuscular and Intravenous Administration: A Pilot Stud

2020 ◽  
Author(s):  
Safoura Beik Rassouli ◽  
Mohammad Reza Rouini ◽  
Farhad Najmeddin ◽  
Azin Gheimati ◽  
Ali A Golabchifar ◽  
...  
Keyword(s):  
Pain Management ◽  
Critically Ill ◽  
Intravenous Administration ◽  
Critically Ill Patients ◽  
Half Life ◽  
Serum Levels ◽  
Volume Of Distribution ◽  
Icu Patients ◽  
Potential Alternative ◽  
Pharmacokinetic Behavior

Background: Methadone is used for the pain management worldwide. Its special characteristics make it a potential alternative for pain management in critically ill and geriatric patients. Due to lack of studies in this population, we aimed to compare the pharmacokinetic behavior of Methadone following intramuscular and intravenous administration in geriatric ICU patients and with previously reports in healthy volunteers. Methods: According to the limitations in ICU setting, we could include 11 patients over 65 years old, who required opioid for pain relief in this study. Patients were randomized to receive 5 mg of Methadone IM or IV injection every 8 hours for 6 days. The Methadone plasma level detected with LC-mass tandem mass spectrometry, and pharmacokinetics parameters were evaluated for each subject in both 1st and 6th days of treatment. Results: Based on our results, bioavailability of intramuscular Methadone in geriatric ICU patients was low and less than 40% of the dose was absorbed within first 12 hours. The volume of distribution of Methadone in the first day was significantly lower than the previously reported values in healthy subjects and significantly increased during these 6 days. The Methadone half-life in this population also significantly increased through this period. Conclusion: Pharmacokinetic behavior of Methadone in geriatric ICU patients is unpredictable. Reduced volume of distribution and half-life may be observed initially, following with an increase to the normal range. It seems that IM administration of Methadone in geriatric critically ill patients may not provide target analgesic Methadone serum levels.

scholarly journals Suboptimal Dosing of Fluconazole in Critically Ill Patients: Time To Rethink Dosing

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Eline W. Muilwijk ◽  
Dylan W. de Lange ◽  
Jeroen A. Schouten ◽  
Roeland E. Wasmann ◽  
Rob ter Heine ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Therapeutic Drug ◽  
Open Label ◽  
Time Curve ◽  
Icu Patients ◽  
Unbound Fraction ◽  
Multicenter Observational Study ◽  
The Impact

ABSTRACT Fluconazole is frequently used for the treatment of invasive Candida infections in critically ill patients. However, alterations in renal functions might influence fluconazole clearance. Therefore, our objective was to study the impact of renal function on the population pharmacokinetics of fluconazole in critically ill patients with various degrees of renal function or undergoing continuous renal replacement therapy (CRRT). This was an open-label, multicenter observational study. Critically ill patients receiving fluconazole were included. Baseline and clinical data were collected. At days 3 and 7 of enrollment, blood samples were drawn for pharmacokinetic curves. Additionally, daily trough samples were taken. A nonlinear mixed-effects model was built, followed by Monte Carlo simulations for assessment of exposure to various dosages of fluconazole. Nineteen patients were included with a median age of 64.4 (range, 23 to 81) years and median weight of 82.0 (range, 44.0 to 119.5) kg. A linear two-compartment model best described fluconazole pharmacokinetics and demonstrated higher clearance than expected in critically ill patients. Simulations showed that daily dosages of 600 mg and 800 mg are needed for intensive care unit (ICU) patients with normal renal function and patients on CRRT, respectively, to achieve the EUCAST-recommended target fAUC (area under the concentration-time curve for the free, unbound fraction of the drug)/MIC ratio of 100. In conclusion, fluconazole clearance is highly variable in ICU patients and is strongly dependent on renal function and CRRT. Trough concentrations correlated well with the AUC, opening up opportunities for tailored dosing using therapeutic drug monitoring. We recommend doses of 400 mg for patients with poor to moderate renal function, 600 mg for patients with adequate renal function, and 800 mg for patients treated with CRRT. (This study has been registered at ClinicalTrials.gov under identifier NCT02666716.)

scholarly journals Individualization of Piperacillin Dosing for Critically Ill Patients: Dosing Software To Optimize Antimicrobial Therapy

2014 ◽  
Vol 58 (7) ◽  
pp. 4094-4102 ◽  
Author(s):  
T. W. Felton ◽  
J. A. Roberts ◽  
T. P. Lodise ◽  
M. Van Guilder ◽  
E. Boselli ◽  
...  
Keyword(s):  
Linear Regression ◽  
Creatinine Clearance ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Volume Of Distribution ◽  
Drug Clearance ◽  
Dose Optimization ◽  
Optimization Software ◽  
The Impact

ABSTRACTPiperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated anr2of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.

scholarly journals Acinetobacterinfections: a growing threat for critically ill patients

2007 ◽  
Vol 136 (8) ◽  
pp. 1009-1019 ◽  
Author(s):  
M. E. FALAGAS ◽  
E. A. KARVELI ◽  
I. I. SIEMPOS ◽  
K. Z. VARDAKAS
Keyword(s):  
United States ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Relative Frequency ◽  
The United States ◽  
Considerable Proportion ◽  
Southern Europe ◽  
Icu Patients

SUMMARYThere has been increasing concern regarding the rise ofAcinetobacterinfections in critically ill patients. We extracted information regarding the relative frequency ofAcinetobacterpneumonia and bacteraemia in intensive-care-unit (ICU) patients and the antimicrobial resistance ofAcinetobacterisolates from studies identified in electronic databases.Acinetobacterinfections most frequently involve the respiratory tract of intubated patients andAcinetobacterpneumonia has been more common in critically ill patients in Asian (range 4–44%) and European (0–35%) hospitals than in United States hospitals (6–11%). There is also a gradient in Europe regarding the proportion of ICU-acquired pneumonias caused byAcinetobacterwith low numbers in Scandinavia, and gradually rising in Central and Southern Europe. A higher proportion ofAcinetobacterisolates were resistant to aminoglycosides and piperacillin/tazobactam in Asian and European countries than in the United States. The data suggest thatAcinetobacterinfections are a growing threat affecting a considerable proportion of critically ill patients, especially in Asia and Europe.

The Concerns of Recovery Practitioners Assisting in the Care of ICU Patients

2001 ◽  
Vol 2 (3-4) ◽  
pp. 6-8 ◽  
Author(s):  
Lynn Sealey
Keyword(s):  
Intensive Care ◽  
Intensive Care Units ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Training And Development ◽  
Small Study ◽  
Icu Patients ◽  
Recovery Unit ◽  
High Dependency

When high dependency and intensive care units are full, which occurs more and more often nationally, recovery wards are being utilised to hold critically ill patients. Recovery practitioners are often expected to assist in the care of these patients.A small study established the views of a sample of recovery practitioners regarding the recovery unit being used as stop-gap, or ICU overflow. There were positive and negative opinions from recovery practitioners who were involved in the care of these critically ill patients. Recovery practitioners often reported feeling inexperienced and ill equipped, with increased levels of stress when working in the ICU bay. Only 20% of recovery practitioners in the study, expressed optimism about working in the ICU bay, and 60% identified that training and development was a strategy which may help to overcome some of their perceived problems.This paper reports these concerns and identifies strategies which have been implemented to address some of these concerns.

scholarly journals Study on Intensive Care Unit Nutritional Protocol Based on Timing of National Health Insurance Coverage in Taiwan

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 850-850
Author(s):  
Shih-Ching Lo ◽  
Yu-Chin Hsiao ◽  
Ying-Ru Chen ◽  
Hsing-Chun Lin
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Health Insurance ◽  
Critically Ill ◽  
National Health Insurance ◽  
National Health ◽  
Critically Ill Patients ◽  
Nutritional Intervention ◽  
Icu Patients ◽  
Nutritional Care

Abstract Objectives Aggressive nutritional intervention may improve the outcomes of critically ill patients. Therefore, the National Health Insurance Administration (NHIA) in Taiwan revised its relevant fee schedule. On October 1, 2019, nutritional care items for intensive care unit (ICU) patients, covered by the NHIA under the category of nutritional care fees, were introduced to reflect real clinical needs. Methods This retrospective cohort study was conducted in a medical center ICU. The study period was January 1, 2019 to May 31, 2020, before and after the start of national health insurance (NHI) coverage of new nutritional care items for ICU patients. A total of 5292 patients were recruited and divided into two groups based on timing of NHI coverage. There were 1591 patients included in the analysis (751 in the non-NHI group and 840 in the NHI group). In the NHI group, the following nutritional protocol was implemented: First visit was at 48hr following admission to the ICU with 2 follow up visits over the next 5 days, then 3 visits the following week. Patient demographics, daily nutritional data, and outcomes were collected to investigate the impact of this protocol. Results Both groups were given the same nutritional intervention initially. However, there were significant differences in nutritional intervention following the incorporation of this treatment protocol in the ICU. Closely monitored nutritional intervention met critical requirements without overfeeding and led to shorter ICU stays (non-NHI 8.11 ± 6.69 days vs NHI 7.12 ± 7.43 days, p &lt; 0.01). Conclusions Nutritional care plan based on frequent assessments and interventions by dietitians is associated with reduced ICU stays for critically ill patients. Funding Sources None.

scholarly journals Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study

2021 ◽  
Vol 12 ◽  
Author(s):  
François Mallet ◽  
Léa Diouf ◽  
Boris Meunier ◽  
Magali Perret ◽  
Frédéric Reynier ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Wilcoxon Test ◽  
Icu Patients ◽  
Prospective Longitudinal Study ◽  
Severity Scores ◽  
Prospective Longitudinal

IntroductionWe analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill patients who had presented with either sepsis, burns, severe trauma, or major surgery. The aim was to identify common features related to virus and injury-associated pathologies and specific features linking one or several viruses to a particular pathological context.MethodsOverall and individual viral DNAemia were measured over a month using quantitative PCR assays from the 377 patients in the REALISM cohort. These patients were characterised by clinical outcomes [severity scores, mortality, Intensive Care Unit (ICU)-acquired infection (IAI)] and 48 parameters defining their host response after injury (cell populations, immune functional assays, and biomarkers). Association between viraemic event and clinical outcomes or immune markers was assessed using χ2-test or exact Fisher’s test for qualitative variables and Wilcoxon test for continuous variables.ResultsThe cumulative incidence of viral DNAemia increased from below 4% at ICU admission to 35% for each herpesvirus during the first month. EBV, HSV1, HHV6, and CMV were detected in 18%, 12%, 10%, and 9% of patients, respectively. The incidence of high TTV viraemia (&gt;10,000 copies/ml) increased from 11% to 15% during the same period. Herpesvirus viraemia was associated with severity at admission; CMV and HHV6 viraemia correlated with mortality during the first week and over the month. The presence of individual herpesvirus during the first month was significantly associated (p &lt; 0.001) with the occurrence of IAI, whilst herpesvirus DNAemia coupled with high TTV viraemia during the very first week was associated with IAI. Herpesvirus viraemia was associated with a lasting exacerbated host immune response, with concurrent profound immune suppression and hyper inflammation, and delayed return to immune homeostasis. The percentage of patients presenting with herpesvirus DNAemia was significantly higher in sepsis than in all other groups. Primary infection in the hospital and high IL10 levels might favour EBV and CMV reactivation.ConclusionIn this cohort of ICU patients, phenotypic differences were observed between TTV and herpesviruses DNAemia. The higher prevalence of herpesvirus DNAemia in sepsis hints at further studies that may enable a better in vivo understanding of host determinants of herpesvirus viral reactivation. Furthermore, our data suggest that EBV and TTV may be useful as additional markers to predict clinical deterioration in ICU patients.

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