Monitoring of sedation depth in intensive care unit by therapeutic drug monitoring? A prospective observation study of medical intensive care patients

Abstract Background Therapeutic drug monitoring (TDM) is a powerful tool to optimize antibiotic exposure. It seldom has been used for β-lactams (BLs). We present our BL data in patients admitted to the surgical intensive care unit (SICU). Methods This retrospective study included SICU patients at UF Health (2016 and 2018) who received BL therapy and had TDM. Data collected included demographics, APACHE scores, platelet count, serum creatinine (Scr), infection source, cultures/susceptibilities, BL regimens, and plasma concentrations. Clinical cure was defined as resolution of infection-related symptoms at the end of therapy. Microbiologic eradication was defined as eradication of causative organism from the primary source out to 30 days after therapy. Pharmacokinetic and statistical analyses were performed on Phoenix v8.0 and JMP Pro v14. Results A total of 127 patients were included. Table 1 shows the baseline characteristics. The median age was 55 years, and weight was 83 kg. Eighty-three (65%) were male. P. aeruginosa was the most common isolated bacteria (n = 38). Lung was the most common source of infection (n = 50). Table 2 summarizes the median (IQR) doses, infusion times, calculated free trough concentrations (fCmin) of common BLs, and the reported minimum inhibitory concentrations (MICs). Calculated median time above the MIC (fT > MIC) for 66 (52%) patients was 100%. A total of 99 (79%) patients had clinical cure and 67 (61%) patients had microbiologic eradication. For efficacy, the Cmin/MIC ratio predicted the microbiologic eradication in wound infections only (n = 15, OR 1.09 [95% CI 1.01–1.24]). Using stepwise regression, 1-unit increase fT > MIC and APACHE score was associated with 0.84 decrease (P = 0.03) and 0.62 increase (P = 0.004) in days of therapy, respectively. For safety, Figure 2 shows the increase in Scr vs. BL free area under the concentration–time curve from time zero to end of the dosing interval (fAUC0-tau). Cefepime fAUC0-tau predicted neurotoxicity (OR per 20 unit increase 1.08 [95% CI: 1.01–1.18]). Conclusion In SICU patients, increase in fT > MIC was associated with shorter treatment duration, and fAUC0-tau increase was associated with an increase in Scr and incidence of neurotoxicity. TDM is warranted in this population to optimize therapy. Disclosures All Authors: No reported Disclosures.

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S15-3. Interdisciplinary Approach to Anti-Infectious Pharmacotherapy in the Intensive Care Unit through the Therapeutic Drug Monitoring

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics ◽

10.3999/jscpt.43.111 ◽

2012 ◽

Vol 43 (2) ◽

pp. 111-112

Author(s):

Takafumi NAITO ◽

Tatsuya YAGI ◽

Junichi KAWAKAMI

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Interdisciplinary Approach ◽

Therapeutic Drug

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Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Critical Care ◽

10.1186/s13054-020-03397-1 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Dennis Kühn ◽

Carlos Metz ◽

Frederik Seiler ◽

Holger Wehrfritz ◽

Sophie Roth ◽

...

Keyword(s):

Intensive Care ◽

Renal Replacement Therapy ◽

Therapeutic Drug Monitoring ◽

Extracorporeal Membrane Oxygenation ◽

Replacement Therapy ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Serum Concentrations ◽

Icu Patients ◽

Intensive Care Patients

Abstract Background Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

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Therapeutic Drug Monitoring of Gentamicin in Neonatal Intensive Care Unit: Experience in 68 Newborns

Journal of Chemotherapy ◽

10.1080/1120009x.2007.11782443 ◽

2007 ◽

Vol 19 (sup2) ◽

pp. 39-41 ◽

Cited By ~ 4

Author(s):

M. Testa ◽

V. Fanos ◽

V. Martinelli ◽

M. Stronati ◽

M. Mussap ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Therapeutic Drug Monitoring ◽

Neonatal Intensive Care Unit ◽

Drug Monitoring ◽

Neonatal Intensive Care ◽

Therapeutic Drug

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What Are the Current Approaches to Optimising Antimicrobial Dosing in the Intensive Care Unit?

Pharmaceutics ◽

10.3390/pharmaceutics12070638 ◽

2020 ◽

Vol 12 (7) ◽

pp. 638

Author(s):

Ming G. Chai ◽

Menino O. Cotta ◽

Mohd H. Abdul-Aziz ◽

Jason A. Roberts

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Therapeutic Drug Monitoring ◽

Patient Outcomes ◽

Drug Monitoring ◽

Point Of Care ◽

Statistical Modelling ◽

Therapeutic Drug ◽

Dosing Regimens ◽

Point Of Care System

Antimicrobial dosing in the intensive care unit (ICU) can be problematic due to various challenges including unique physiological changes observed in critically ill patients and the presence of pathogens with reduced susceptibility. These challenges result in reduced likelihood of standard antimicrobial dosing regimens achieving target exposures associated with optimal patient outcomes. Therefore, the aim of this review is to explore the various methods for optimisation of antimicrobial dosing in ICU patients. Dosing nomograms developed from pharmacokinetic/statistical models and therapeutic drug monitoring are commonly used. However, recent advances in mathematical and statistical modelling have resulted in the development of novel dosing software that utilise Bayesian forecasting and/or artificial intelligence. These programs utilise therapeutic drug monitoring results to further personalise antimicrobial therapy based on each patient’s clinical characteristics. Studies quantifying the clinical and cost benefits associated with dosing software are required before widespread use as a point-of-care system can be justified.

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Therapeutic Drug Monitoring in the Pediatric Intensive Care Unit

Pediatric Clinics of North America ◽

10.1016/s0031-3955(16)38870-8 ◽

1994 ◽

Vol 41 (6) ◽

pp. 1227-1243 ◽

Cited By ~ 6

Author(s):

Michael D. Reed ◽

Jeffrey L. Blumer

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Therapeutic Drug Monitoring ◽

Pediatric Intensive Care Unit ◽

Drug Monitoring ◽

Pediatric Intensive Care ◽

Therapeutic Drug

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Initiation of Vancomycin Therapy and the First Therapeutic Drug Monitoring

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.2478/prolas-2021-0007 ◽

2021 ◽

Vol 75 (1) ◽

pp. 40-46

Author(s):

Inga Mauliņa ◽

Angelika Krūmiņa ◽

Aleksandra Aitullina ◽

Roberts Erts ◽

Katrīna Bandere ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Study Data ◽

Concentration Measurement ◽

Therapeutic Drug ◽

Vancomycin Therapy ◽

Initiation Phase ◽

Subtherapeutic Level

AbstractThere have been a limited number of studies in Latvia that were focused on vancomycin therapeutic drug monitoring (TDM), especially during the initiation phase of the therapy. The aim of this study was to investigate details of vancomycin therapy in its initiation phase and to analyse the results of the first therapeutic drug monitoring within a multidisciplinary hospital in Latvia. A retrospective observational study was performed in a multidisciplinary hospital in Latvia. Adult patients hospitalised in an intensive care unit and undergoing vancomycin therapy with at least one concentration measurement were included in this study. Data about patients included demographic and clinical data, renal function prior to initiation of vancomycin therapy, data about vancomycin therapy, data about the first TDM, and details about the first measurement of vancomycin concentration according to determined reference range — subtherapeutic, therapeutic and supratherapeutic levels. A total of 60 intensive care unit patients who received vancomycin with at least one concentration measurement were included in this study. Fifty-eight patients received vancomycin as intermittent intravenous infusion. The first measurement of concentration was taken before the 3rd–4th vancomycin dose in 38.3% cases, and in 33.3% cases — before the 2nd dose. Sampling to determine the concentration within 30 minutes before vancomycin administration was performed in zero cases. In 35% cases, sampling was done within 2–5 hours before vancomycin administration and in 23.3% — immediately after or within a few hours after vancomycin infusion. Twelve (20%) patients had a concentration in the subtherapeutic level, and 14 (23.3%) patients had concentrations above the therapeutic level. In 42.8% of patients who had concentrations in supratherapeutic level, sampling had been performed immediately after or within several hours after vancomycin administration. The first concentration measurement was performed more than one hour before an infusion in all cases. Data on concentrations and timing were not adequate to perform appropriate therapy modification. Interpretation of dosing regime and concentration results were not adequate, and therefore correct modification of vancomycin therapy was often not possible. Routines of correct dosing regime and the 1st TDM during the initiation phase of vancomycin therapy can be improved.

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