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Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study.

Wen A, Li Z, Yu J, Li R, Cheng S, Duan M, Bai J - PLoS ONE (2016)

Bottom Line: The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001).The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis.No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

ABSTRACT

Objectives: The primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy.

Methods: A prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated.

Results: Eighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.

Conclusion: Spent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients.

No MeSH data available.


Related in: MedlinePlus

Bland-Altman plot of plasma/effluent concentration ratios compared to average plasma and effluent concentrations (n = 83).The line representing the bias is presented as a solid line, and the 95% limits of agreement are presented as dashed lines. The bias is 1.044 (95% CI, 0.975 to 1.114), and the lower and upper 95% limits of agreement are 0.417 (95% CI, 0.298 to 0.537) and 1.671 (95% CI, 1.552 to 1.791).
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pone.0153927.g002: Bland-Altman plot of plasma/effluent concentration ratios compared to average plasma and effluent concentrations (n = 83).The line representing the bias is presented as a solid line, and the 95% limits of agreement are presented as dashed lines. The bias is 1.044 (95% CI, 0.975 to 1.114), and the lower and upper 95% limits of agreement are 0.417 (95% CI, 0.298 to 0.537) and 1.671 (95% CI, 1.552 to 1.791).

Mentions: Eighty-three paired plasma and effluent samples from 10 patients were included in the clinical validation of the effluent analysis. The Pearson correlation showed a correlation coefficient of 0.950 (P<0.0001) for the imipenem concentrations in plasma and effluent. Passing-Bablok regression between the plasma and effluent imipenem concentrations showed a proportional bias of 0.997 (95% confidence interval [CI], 0.935 to 1.078) and a constant bias of -0.039 (95% CI, -0.514 to 0.247) (Fig 1). A linear relationship between plasma and effluent imipenem concentrations was indicated by the Cusum linearity test (P>0.10). Bland-Altman assessment showed a good agreement between analyses of imipenem concentrations in plasma and effluent, with 4.8% (4/83) of observations for imipenem falling outside 95% limits of agreement (Fig 2). The observed bias for the mean plasma-to-effluent imipenem concentration ratio versus the mean concentration in plasma and effluent was 1.044 (95% CI, 0.975 to 1.114, Fig 2).


Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study.

Wen A, Li Z, Yu J, Li R, Cheng S, Duan M, Bai J - PLoS ONE (2016)

Bland-Altman plot of plasma/effluent concentration ratios compared to average plasma and effluent concentrations (n = 83).The line representing the bias is presented as a solid line, and the 95% limits of agreement are presented as dashed lines. The bias is 1.044 (95% CI, 0.975 to 1.114), and the lower and upper 95% limits of agreement are 0.417 (95% CI, 0.298 to 0.537) and 1.671 (95% CI, 1.552 to 1.791).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836878&req=5

pone.0153927.g002: Bland-Altman plot of plasma/effluent concentration ratios compared to average plasma and effluent concentrations (n = 83).The line representing the bias is presented as a solid line, and the 95% limits of agreement are presented as dashed lines. The bias is 1.044 (95% CI, 0.975 to 1.114), and the lower and upper 95% limits of agreement are 0.417 (95% CI, 0.298 to 0.537) and 1.671 (95% CI, 1.552 to 1.791).
Mentions: Eighty-three paired plasma and effluent samples from 10 patients were included in the clinical validation of the effluent analysis. The Pearson correlation showed a correlation coefficient of 0.950 (P<0.0001) for the imipenem concentrations in plasma and effluent. Passing-Bablok regression between the plasma and effluent imipenem concentrations showed a proportional bias of 0.997 (95% confidence interval [CI], 0.935 to 1.078) and a constant bias of -0.039 (95% CI, -0.514 to 0.247) (Fig 1). A linear relationship between plasma and effluent imipenem concentrations was indicated by the Cusum linearity test (P>0.10). Bland-Altman assessment showed a good agreement between analyses of imipenem concentrations in plasma and effluent, with 4.8% (4/83) of observations for imipenem falling outside 95% limits of agreement (Fig 2). The observed bias for the mean plasma-to-effluent imipenem concentration ratio versus the mean concentration in plasma and effluent was 1.044 (95% CI, 0.975 to 1.114, Fig 2).

Bottom Line: The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001).The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis.No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

ABSTRACT

Objectives: The primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy.

Methods: A prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated.

Results: Eighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.

Conclusion: Spent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients.

No MeSH data available.


Related in: MedlinePlus