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 Low Myostatin Serum Levels Are Associated with Poor Outcome in Critically Ill Patients

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 574
Author(s):  
Theresa H. Wirtz ◽  
Sven H. Loosen ◽  
Lukas Buendgens ◽  
Berkan Kurt ◽  
Samira Abu Jhaisha ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Regression ◽  
Muscle Growth ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Icu Patients ◽  
Cox Regression Analysis ◽  
Independent Prognostic Marker ◽  
Unfavorable Clinical Outcome

Background: Growth differentiation factor 8, GDF-8 (Myostatin), is a protein released by myocytes inhibiting muscle growth and differentiation. Serum concentrations of Myostatin can predict poor survival in different chronic diseases, but its role in critical illness and sepsis is obscure. Our aim was to investigate Myostatin levels as a potential prognostic biomarker in critically ill patients with sepsis. Methods: We therefore measured Myostatin serum concentrations in 165 critically ill patients (106 with sepsis, 59 without sepsis) upon admission to the medical intensive care unit (ICU), in comparison to 14 healthy controls. Results: Myostatin levels were significantly decreased in ICU patients compared to controls but did not differ in patients with or without sepsis. However, Myostatin concentrations were significantly lower in patients requiring mechanical ventilation and indicated a trend towards dependency of intravenous vasopressors. Interestingly, we observed a negative correlation between Myostatin levels and markers of systemic inflammation. Strikingly, overall survival (OS) was significantly impaired in patients with low Myostatin levels in all critically ill patients. Low Myostatin levels at baseline turned out as an independent prognostic marker for OS in multivariate Cox-regression analysis (HR: 0.433, 95% CI: 0.211–0.889, p = 0.023). Conclusions: In summary, serum Myostatin concentrations are significantly decreased in critically ill patients and associated with disease severity. Low Myostatin levels also identify a subgroup of ICU patients that are more likely to face an unfavorable clinical outcome in terms of OS.

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 High Circulating Caspase-Cleaved Keratin 18 Fragments (M30) Indicate Short-Term Mortality in Critically Ill Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Alexander Koch ◽  
Eray Yagmur ◽  
Janine Linka ◽  
Fabienne Schumacher ◽  
Jan Bruensing ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Cell Injury ◽  
Serum Levels ◽  
Intermediate Filament Protein ◽  
Healthy Controls ◽  
Short Term ◽  
Icu Patients ◽  
Short Term Mortality ◽  
Keratin 18

Caspase-cleaved fragments of the intermediate filament protein keratin 18 (cytokeratin-18 (CK18)) can be detected in serum as M30 levels and may serve as a circulating biomarker indicating apoptosis of epithelial and parenchymal cells. In order to evaluate M30 as a biomarker in critical illness, we analyzed circulating M30 levels in 243 critically ill patients (156 with sepsis, 87 without sepsis) at admission to the medical intensive care unit (ICU), in comparison to healthy controls (n=32). M30 levels were significantly elevated in ICU patients compared with healthy controls. Circulating M30 was closely associated with disease severity but did not differ between patients with sepsis and ICU patients without sepsis. M30 serum levels were correlated with biomarkers of inflammation, cell injury, renal failure, and liver failure in critically ill patients. Patients that died at the ICU showed increased M30 levels at admission, compared with surviving patients. A similar trend was observed for the overall survival. Regression analyses confirmed that M30 levels are associated with mortality, and patients with M30 levels above 250.8 U/L displayed an excessive short-term mortality. Thus, our data support the utility of circulating levels of the apoptosis-related keratin fragment M30 as a prognostic biomarker at ICU admission.

scholarly journals Circulating MicroRNA-223 Serum Levels Do Not Predict Sepsis or Survival in Patients with Critical Illness

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Fabian Benz ◽  
Frank Tacke ◽  
Mark Luedde ◽  
Christian Trautwein ◽  
Tom Luedde ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Responses ◽  
Elevated Serum ◽  
Serum Levels ◽  
Apache Ii Score ◽  
Circulating Microrna ◽  
Icu Patients ◽  
Markers Of Inflammation

Background and Aims. Dysregulation of miR-223 was recently linked to various diseases associated with systemic inflammatory responses such as type 2 diabetes, cancer, and bacterial infections. However, contradictory results are available on potential alterations of miR-223 serum levels during sepsis. We thus aimed to evaluate the diagnostic and prognostic value of miR-223 serum concentrations in patients with critical illness and sepsis.Methods. We used i.v. injection of lipopolysaccharide (LPS) as well as cecal pole ligation and puncture (CLP) for induction of polymicrobial sepsis in mice and measured alterations in serum levels of miR-223. These results from mice were translated into a large and well-characterized cohort of critically ill patients admitted to the medical intensive care unit (ICU). Finally, results from analysis in patients were correlated with clinical data and extensive sets of routine and experimental biomarkers.Results. Although LPS injection induced moderately elevated serum miR-223 levels in mice, no significant alterations in miR-223 serum levels were found in mice after CLP-induced sepsis. In accordance with these results from animal models, serum miR-223 levels did not differ between critically ill patients and healthy controls. However, ICU patients with more severe disease (APACHE-II score) showed moderately reduced circulating miR-223. Strikingly, no differences in miR-223 levels were found in critically ill patients with or without sepsis, and serum levels of miR-223 did not correlate with classical markers of inflammation or bacterial infection. Finally, low miR-223 serum levels were moderately associated with an unfavorable prognosis of patients during the ICU treatment but did not predict long-term mortality.Conclusion. Recent reports on alterations in miR-223 serum levels during sepsis revealed contradictory results, preventing a potential use of this miRNA in clinical routine. We clearly show that miR-223 serum levels do not reflect the presence of sepsis neither in mouse models nor in a large cohort of ICU patients and do not indicate clinical outcome of critically ill patients. Thus miR-223 serum levels should not be used as a biomarker in this setting.

scholarly journals Evaluation of Amikacin Pharmacokinetics in Critically Ill Patients with Intra-abdominal Sepsis

2019 ◽  
Vol 10 (1) ◽  
pp. 114-118
Author(s):  
Bita Shahrami ◽  
Farhad Najmeddin ◽  
Mohammad Reza Rouini ◽  
Atabak Najafi ◽  
Kourosh Sadeghi ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Half Life ◽  
Abdominal Sepsis ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Significant Difference ◽  
Group 2 ◽  
Intraabdominal Sepsis ◽  
Group 1

Purpose: Although the current widespread use of amikacin is in intra-abdominal sepsis treatment, its pharmacokinetic changes in the present setting are not yet well known. This study was aimed to evaluate the amikacin pharmacokinetic profile in critically ill patients with intraabdominal sepsis compared to pneumosepsis. Methods: Adult septic patients received amikacin therapy were studied. Patients with intraabdominal sepsis were enrolled in group 1 (n=16), and patients with pneumosepsis were enrolled in group 2 (n=13). The amikacin serum concentrations were evaluated in the first, second, fourth and sixth hours after initiating 30-minute infusion. The pharmacokinetic parameters were calculated for each patient. Results: There was no significant difference in the volume of distribution between the two groups (0.33±0.08 vs. 0.28±0.10 L/kg, P=0.193). The amikacin clearance was significantly lower in group 1 compared to group 2 (58.5±21.7 vs. 83.9±37.0 mL/min, P=0.029). There was no significant correlation between amikacin clearance and creatinine clearance estimated by Cockcroft-Gault formula in all patients (P=0.206). The half-life was significantly longer in group 1 compared to group 2 (5.3±2.8 vs. 3.4±3.2 hours, P=0.015). Conclusion: Pathophysiologic changes following intra-abdominal sepsis can affect amikacin pharmacokinetics behavior. The clearance and half-life may change, but the alteration of the volume of distribution is not significantly different in comparison with pneumosepsis. Further studies are required to evaluate the pharmacokinetic variables of amikacin in critically ill patients with intra-abdominal sepsis.

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.

scholarly journals Elevated Omentin Serum Levels Predict Long-Term Survival in Critically Ill Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mark Luedde ◽  
Fabian Benz ◽  
Jennifer Niedeggen ◽  
Mihael Vucur ◽  
Hans-Joerg Hippe ◽  
...  
Keyword(s):  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Term Survival ◽  
Icu Patients ◽  
Icu Treatment

Introduction. Omentin, a recently described adipokine, was shown to be involved in the pathophysiology of inflammatory and infectious diseases. However, its role in critical illness and sepsis is currently unknown. Materials and Methods. Omentin serum concentrations were measured in 117 ICU-patients (84 with septic and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were compared with 50 healthy controls. Results. Omentin serum levels of critically ill patients at admission to the ICU or after 72 hours of ICU treatment were similar compared to healthy controls. Moreover, circulating omentin levels were independent of sepsis and etiology of critical illness. Notably, serum concentrations of omentin could not be linked to concentrations of inflammatory cytokines or routinely used sepsis markers. While serum levels of omentin were not predictive for short term survival during ICU treatment, low omentin concentrations were an independent predictor of patients’ overall survival. Omentin levels strongly correlated with that of other adipokines (e.g., leptin receptor or adiponectin), which have also been identified as prognostic markers in critical illness. Conclusions. Although circulating omentin levels did not differ between ICU-patients and controls, elevated omentin levels were predictive for an impaired patients’ long term survival.

scholarly journals Serum Levels of miR-143 Predict Survival in Critically Ill Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Christoph Roderburg ◽  
Alexander Koch ◽  
Fabian Benz ◽  
Mihael Vucur ◽  
Martina Spehlmann ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Significance ◽  
Serum Levels ◽  
Icu Patients ◽  
Disease Etiology ◽  
Short And Long Term ◽  
Long Term Prognosis ◽  
Clinical Records

Background and Aims. Recent data suggested a potential role of miR-143 as a biomarker for systemic inflammation and infection. However, its role in critical illness and sepsis is only poorly understood. Methods. We determined circulating levels of miR-143 in 218 critically ill patients, of which 135 fulfilled sepsis criteria, and compared them to 76 healthy controls. Results were correlated with clinical records. Results. In the total cohort of critically ill patients from a medical intensive care unit (ICU), miR-143 serum levels tended to be lower compared to healthy control samples, but this difference did not reach statistical significance. In ICU patients, serum levels of miR-143 were independent of disease etiology, including the presence of sepsis, or severity of disease. Importantly, low miR-143 serum levels were associated with an unfavorable short- and long-term prognosis in ICU patients. Our study identified different optimal cut-off values at which low miR-143 serum levels predicted mortality with a high diagnostic accuracy. In line with this, concentrations of circulating miR-143 correlated with markers of organ failure such as creatinine, bilirubin, or lactate in our cohort of critically ill patients. Conclusion. Low miR-143 serum levels are indicative for an unfavorable short- and long-term prognosis in critically ill patients admitted to a medical ICU. Our data suggest a previously unrecognized role for miR-143 measurements as a novel prognostic marker in critically ill patients.

scholarly journals Beta-Lactams Dosing in Critically Ill Patients with Gram-Negative Bacterial Infections: A PK/PD Approach

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1154
Author(s):  
Kelly L. Maguigan ◽  
Mohammad H. Al-Shaer ◽  
Charles A. Peloquin
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Kidney Injury ◽  
Volume Of Distribution ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Icu Patients ◽  
Gram Negative ◽  
Dosing Strategies

Beta-lactam antibiotics are often the backbone of treatment for Gram-negative infections in the critically ill. Beta-lactams exhibit time-dependent killing, and their efficacy depends on the percentage of dosing interval that the concentration remains above the minimum inhibitory concentration. The Gram-negative resistance rates of pathogens are increasing in the intensive care unit (ICU), and critically ill patients often possess physiology that makes dosing more challenging. The volume of distribution is usually increased, and drug clearance is variable. Augmented renal clearance and hypermetabolic states increase the clearance of beta-lactams, while acute kidney injury reduces the clearance. To overcome the factors affecting ICU patients and decreasing susceptibilities, dosing strategies involving higher doses, and extended or continuous infusions may be required. In this review, we specifically examined pharmacokinetic models in ICU patients, to determine the desired beta-lactam regimens for clinical breakpoints of Enterobacterales and Pseudomonas aeruginosa, as determined by the European Committee on Antimicrobial Susceptibility Testing. The beta-lactams evaluated included penicillins, cephalosporins, carbapenems, and monobactams. We found that when treating less-susceptible pathogens, especially P. aeruginosa, continuous infusions are frequently needed to achieve the desired pharmacokinetic/pharmacodynamic targets. More studies are needed to determine optimal dosing strategies in the novel beta-lactams.

Psychological Factors Affecting Pain Response in Critically Ill Patients

2021 ◽  
Vol 1 (2) ◽  
pp. 32-34
Author(s):  
Rani Iswara
Keyword(s):  
Pain Management ◽  
Sleep Deprivation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Psychological Factors ◽  
Multimodal Analgesia ◽  
Traumatic Experience ◽  
Factors Affecting ◽  
Control Pain ◽  
Harmful Effects

Pain is a traumatic experience and discomfort for all patients, especially critically ill patients; if not treated properly, it can have harmful effects. Critical illnesses are usually painful, both because of the underlying source of the disease and the necessary procedures performed to monitor and care for these patients. Pain induces anxiety, sleep deprivation, disorientation, agitation, delirium, and often become chronic depression. Psychological factors (sleep deprivation, anxiety, and delirium) can also increase the perception of pain. Pain assessment is required for proper pain management. Opioids are commonly used in pain management, but acetaminophen, dexmedetomidine, and gabapentin have more advantages. The recent trend is multimodal analgesia, which uses a combination of analgesic drugs with different mechanisms of action. Another trend is the increasing use of pain relievers, which can control pain and relieve anxiety.

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