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 Can the cytokine adsorber CytoSorb® help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Ines Schroeder ◽  
Michael Paal ◽  
Martin Winkels ◽  
Michael Irlbeck ◽  
...  
Keyword(s):  
Propensity Score ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Wilcoxon Test ◽  
Relative Reduction ◽  
Cytokine Storm ◽  
Saps Ii ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

Abstract Background A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. Methods Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables. Results In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). Conclusion Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.

scholarly journals Achievement of Vancomycin Therapeutic Goals in Critically Ill Patients: Early Individualization May Be Beneficial

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Bita Shahrami ◽  
Farhad Najmeddin ◽  
Sarah Mousavi ◽  
Arezoo Ahmadi ◽  
Mohammad Reza Rouini ◽  
...  
Keyword(s):  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Therapeutic Goals ◽  
Dose Monitoring ◽  
Trough Serum ◽  
Group 2 ◽  
Group 1

Objective.The aim of our study was to assess and validate the effectiveness of early dose adjustment of vancomycin based on first dose monitoring in achieving target recommended goal in critically ill patients.Methods.Twenty critically ill patients with sepsis received loading dose of 25 mg/kg of vancomycin and then were randomly assigned to 2 groups. Group 1 received maximum empirical doses of vancomycin of 15 mg/kg every 8 hrs. In group 2, the doses were individualized based on serum concentrations of vancomycin. First dose nonsteady state sampling was used to calculate pharmacokinetic parameters of the patients within 24 hours.Results.Steady state trough serum concentrations were significantly higher in group 2 in comparison with group 1 (19.4 ± 4.4 mg/L versus 14.4 ± 4.3 mg/L) (P=0.03). Steady state AUCs were significantly higher in group 2 compared with group 1 (665.9 ± 136.5 mg·hr/L versus 490.7 ± 101.1 mg·hr/L) (P=0.008).Conclusions.With early individualized dosing regimen, significantly more patients achieved peak and trough steady state concentrations. In the context of pharmacokinetic/pharmacodynamic goal of area under the time concentration curve to minimum inhibitory concentration (AUC/MIC) ≥400 and also to obtain trough serum concentration of vancomycin of ≥15 mg/L, it is necessary to individualize doses of vancomycin in critically ill patients.

scholarly journals Effects of fenugreek seed powder on enteral nutrition tolerance and clinical outcomes in critically ill patients: A randomized clinical trial

2018 ◽  
Vol 5 (7) ◽  
pp. 2528-2537
Author(s):  
Akram Kooshki ◽  
Zaher Khazaei ◽  
Azam Zarghi ◽  
Mojtaba Rad ◽  
Hadi Gholam Mohammadi ◽  
...  
Keyword(s):  
Enteral Nutrition ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Routine Care ◽  
Fenugreek Seeds ◽  
Mechanically Ventilated ◽  
Fenugreek Seed ◽  
Group 2 ◽  
Group 1

Background: Enteral nutrition (EN) intolerance is a common complication in critically ill patients that contributes to morbidity and mortality. Based on the evidence of curing effects of fenugreek seeds in some gastrointestinal disorders, this study aimed to determine the effects of fenugreek seed powder on enteral nutrition tolerance and clinical outcomes in critically ill patients. Materials & Methods: A randomized, double-blinded clinical trial of 5-day duration was conducted on 60 mechanically ventilated patients divided in 2 groups (n=30). Group 1 was given fenugreek seed powder by gavage, twice a day in addition to routine care, while Group 2 received only routine care. Enteral nutrition tolerance and clinical outcomes were measured throughout the study. Demographic and clinical data were recorded and clinical responses to the primary outcome (enteral nutrition tolerance) and secondary outcome (other clinical factors) were interpreted. Data were analyzed using the independent t-test, Chi-squared test, covariance analysis, and repeated measure ANOVA via SPSS statistical software (v. 20); statistical significance was set at p< 0.05. Results: Patients who were fed with the fenugreek seed powder showed a significant improvement in enteral nutrition tolerance, as well as some complications of mechanical ventilation for Group 1, as compared with Group 2. The mortality rates were not different between the two groups. Conclusion: This study shows the beneficial effects of fenugreek seeds on food intolerance in critically ill patients and that the seed powder can be used as an add-on therapy with other medications. Thus, the use of fenugreek seeds to treat mechanically ventilated patients is recommended.

Evaluation of Intravenous Phenobarbital Pharmacokinetics in Critically Ill Patients With Brain Injury

2022 ◽  
Author(s):  
Seyedeh Sana Khezrnia ◽  
Bita Shahrami ◽  
Mohammad Reza Rouini ◽  
Atabak Najafi ◽  
Hamid Reza Sharifnia ◽  
...  
Keyword(s):  
Brain Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Population ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Uv Detector ◽  
Therapeutic Goals ◽  
The Impact

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.

scholarly journals Prospectively Validated Dosing Nomograms for Maximizing the Pharmacodynamics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients

2009 ◽  
Vol 53 (5) ◽  
pp. 1863-1867 ◽  
Author(s):  
Federico Pea ◽  
Mario Furlanut ◽  
Camilla Negri ◽  
Federica Pavan ◽  
Massimo Crapis ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Dosage Calculation ◽  
Cohort Group ◽  
Increased Risk ◽  
Dependent Activity ◽  
Group 2 ◽  
Vancomycin Treatment ◽  
Group 1

ABSTRACT The efficacy of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA)-related infections has been called into question by recent findings of higher rates of failure of vancomycin treatment of infections caused by strains with high MICs. Continuous infusion may be the best way to maximize the time-dependent activity of vancomycin. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CLCr) estimates for use in daily clinical practice to target the steady-state concentrations (C sss) of vancomycin during continuous infusion at 15 to 20 mg/liter (after the administration of an initial loading dose of 15 mg/kg of body weight over 2 h). The correlation between vancomycin clearance (CLv) and CLCr was retrospectively assessed in a cohort of critically ill patients (group 1, n = 70) to create a formula for dosage calculation to target C ss at 15 mg/liter. The performance of this formula was prospectively validated in a similar cohort (group 2, n = 63) by comparison of the observed and the predicted C sss. A significant relationship between CLv and CLCr was observed in group 1 (P < 0.001). The application of the calculated formula to vancomycin dosing in group 2 {infusion rate (g/24 h) = [0.029 × CLCr (ml/min) + 0.94] × target Css × (24/1,000)} led to a significant correlation between the observed and the predicted C sss (r = 0.80, P < 0.001). Two dosing nomograms based on CLCr were created to target the vancomycin C ss at 15 and 20 mg/liter in critically ill patients. These nomograms could be helpful in improving the vancomycin treatment of MRSA infections, especially in the presence of borderline-susceptible pathogens and/or of pathophysiological conditions which may enhance the clearance of vancomycin, while potentially avoiding the increased risk of nephrotoxicity observed with the use of high intermittent doses of vancomycin.

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 The Influence of Age on Lignocaine Pharmacokinetics in Young Puppies

1986 ◽  
Vol 14 (2) ◽  
pp. 135-139 ◽  
Author(s):  
C. L. Hastings ◽  
T. C. K. Brown ◽  
R. L. Eyres ◽  
R. C. Oppenheim
Keyword(s):  
Age Groups ◽  
Elimination Rate ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Group 4 ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Eight mongrel puppies were studied at intervals of a few weeks. Lignocaine 4mg/kg was infused over 60 seconds. Frequent samples were taken over 30 minutes for plasma lignocaine assay. Initially the concentrations were significantly higher in the oldest group (178–191 days) but after 10 minutes the youngest group (3–16 days) had significantly higher levels than the other groups. Pharmacokinetic data derived included the rate constants k21, k12 (drug movement between two compartments), k10 (elimination from the central compartment), and the volume of distribution (Vβ). The elimination rate constant k10 was significantly lower in Group 1 (3–16 days) than all other groups and Group 2 (37–57 days) was lower than Group 4 (178–191 days). The calculated β half-life was significantly longer in the youngest group than the others. There was no significant difference in the volume of distribution between these age groups — up to 6 months.

scholarly journals The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Christina Scharf ◽  
Uwe Liebchen ◽  
Michael Paal ◽  
Max Taubert ◽  
Michael Vogeser ◽  
...  
Keyword(s):  
Liver Function ◽  
Hospital Mortality ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Beta Lactam ◽  
Target Attainment ◽  
Outcome Group ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Objectives Beta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment. Methods An outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration (f) was < 100% of the time (T) above the minimal inhibitory concentration (MIC) (< 100% fT >MIC), group 2=100% fT >MIC<4xMIC, and group 3=100% fT >4xMIC. Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test, U test, and bivariate logistic regression. Results The outcome group consisted of 55 patients (groups 1–3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 (p = 0.033 and p = 0.026). Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 (p = 0.017) and group 2 (p = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy. Conclusion Achieving the target 100% fT >MIC leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT >4xMIC, although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT >MIC<4xMIC for critically ill patients. Trial registration NCT03985605

scholarly journals Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach

2012 ◽  
Vol 56 (12) ◽  
pp. 6343-6348 ◽  
Author(s):  
Federico Pea ◽  
Pierluigi Viale ◽  
Piergiorgio Cojutti ◽  
Mario Furlanut
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Gram Negative ◽  
Content Type ◽  
Dosage Calculation ◽  
Cohort Group ◽  
Dependent Activity ◽  
Group 2 ◽  
Group 1

ABSTRACTThe worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producingEnterobacteriaceaehas significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CLCr) estimates for use in daily clinical practice to target the steady-state concentrations (Csss) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CLm) and CLCrwas retrospectively assessed in a cohort of critically ill patients (group 1,n= 67) to create a formula for dosage calculation to targetCss. The performance of this formula was validated in a similar cohort (group 2,n= 56) by comparison of the observed and the predictedCsss. A significant relationship between CLmand CLCrwas observed in group 1 (r= 0.72,P< 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CLCr(ml/min) + 2.85] × targetCss× (24/1,000), led to a significant correlation between the observed and the predictedCsss (r= 0.92,P< 0.001). Dosing nomograms based on CLCrwere created to target the meropenemCssat 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance.

scholarly journals Reduction of Intra-abdominal Hypertension Is Associated with Increase of Cardiac Output in Critically Ill Patients Undergoing Mechanical Ventilation

2018 ◽  
Vol 3 (2) ◽  
pp. 90-97
Author(s):  
Claudiu Puiac ◽  
Theodora Benedek ◽  
Lucian Puscasiu ◽  
Nora Rat ◽  
Emoke Almasy ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Abdominal Pressure ◽  
Mechanically Ventilated ◽  
Mechanically Ventilated Patients ◽  
Abdominal Hypertension ◽  
Group 2 ◽  
Ventilated Patients ◽  
Group 1

Abstract Objective: To demonstrate the relationship between intra-abdominal hypertension (IAH) and cardiac output (CO) in mechanically ventilated (MV), critically ill patients. Material and methods: This was a single-center, prospective study performed between January and April 2016, on 30 mechanically ventilated patients (mean age 67.3 ± 11.9 years), admitted in the Intensive Care Unit (ICU) of the Emergency County Hospital of Tîrgu Mureș, Romania, who underwent measurements of intra-abdominal pressure (IAP). Patients were divided into two groups: group 1 – IAP <12 mmHg (n = 21) and group 2 – IAP >12 mmHg (n = 9). In 23 patients who survived at least 3 days post inclusion, the variation of CO and IAP between baseline and day 3 was calculated, in order to assess the variation of IAP in relation to the hemodynamic status. Results: IAP was 8.52 ± 1.59 mmHg in group 1 and 19.88 ± 8.05 mmHg in group 2 (p <0.0001). CO was significantly higher in group 1 than in the group with IAH: 6.96 ± 2.07 mmHg (95% CI 6.01–7.9) vs. 4.57 ± 1.23 mmHg (95% CI 3.62–5.52) (p = 0.003). Linear regression demonstrated an inverse correlation between CO and IAP (r = 0.48, p = 0.007). Serial measurements of CO and IAP proved that whenever accomplished, the decrease of IAP was associated with a significant increase in CO (p = 0.02). Conclusions: CO is significantly correlated with IAP in mechanically ventilated patients, and IAH reduction is associated with increase of CO in these critically ill cases.

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