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A1053
October 20, 2009 8:00 AM - 9:30 AM Room Room 356 |
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| Plasma Mannitol Assay and Its Population Pharmacokinetic Modeling | ||||||||||||||||||||||||||||||
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Tae-Hyung Han, M.D., Ph.D., Kotaro Kaneda, M.D., Max T. Baker, Ph.D. Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, Iowa |
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Introduction:
Mannitol has been used to treat cerebral edema and intracranial hypertension in neurosurgical patients. It is typically given as an intermittent single bolus (0.5-1.0 gm/kg) repeated over hours or days. This can lead to oscillation of super and subtherapeutic serum osmolality. Continuous infusion, maintaining target serum osmolality, may improve the therapy. The study objective was to delineate population pharmacokinetics of a single bolus of 20% mannitol.
Methods: Patients, scheduled for elective craniotomy for brain tumor extirpation and anticipated to receive hyperosmotic agent intraoperatively, were enrolled. They received 20% mannitol 1 g/kg (n=9) over 15 min by a volumetric pulsatile infusion pump. This approximated an osmotic loading of 5 mOsm/kg. Serial plasma mannitol concentrations were collected over 12 hr period and analyzed by gas chromatograph with FID mode. NONMEM® was employed for compartmental modeling. Results: Raw data scattered across the wide range.[figure1]Tri-exponential compartmental model well described plasma mannitol concentration decay over time (OFV = -61.0).[figure2]Estimated population parameters were summarized.[table1]The mean maximal plasma concentration was 7.2 mg/ml at the end of infusion and decreased to 0.9 mg/ml. The plasma initial, re-distribution and terminal half-lives were 0.1, 18.8 minutes and 4.0 hours, respectively. Large coefficient of variation in V1 suggested significant inter-individual variability. Pharmacokinetic parameters were unchanged when different doses were administered. Weight was an important covariate influencing the model performance. Conclusion: Three-compartment pharmacokinetic model best described the disposition characteristics of mannitol. The osmolar system was linear, i.e., dose dependent. Accordingly, the serum osmolality can be predicted, in proportion to the given dose. Data obtained from single bolus administration of mannitol should be carefully interpreted prior to implementing a continuous infusion regimen since the long term effect is unknown. Further study is needed to accomplish a safe and effective clinical application using the current population pharmacokinetic model for mannitol. From Proceedings of the 2009 Annual Meeting of the American Society Anesthesiologists. |
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Figure 1
 Figure 2  |