Dopamine May Decrease Nephrotoxicity in Patients Receiving High-Dose Ifosfamide

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´╗┐Dopamine May Decrease Nephrotoxicity in Patients Receiving High-Dose Ifosfamide L Johnetta Blakely, SR Patel, PF Thall, X Wang, TA Simmons, JL Beach, TL Armen, LL Chen, MA Burgess, JC Trent, and RS Benjamin UT MD Anderson Cancer Center Houston, United States

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Background Ifosfamide is a standout amongst the most ordinarily utilized and best chemotherapeutic operators for sarcoma Complications with high-measurements ifosfamide: Renal Toxicity Neurotoxicity Neutropenia/Fever

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Background Dopamine Low dosages have been appeared to expand blood stream and GFR Some confirmation recommends a renal defensive impact in disease patients getting immunotherapy

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Giving Dopamine with Ifosfamide: Rationale and Possible Benefits Decrease in "subclinical" nephrotoxicity Decrease in clinical nephrotoxicity Decrease in other antagonistic reactions Decrease long of doctor's facility stay Increase in the underlying measurement and perhaps resulting dosages of ifosfamide Increase in cure rate and expected survival

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Methods Randomized stage III study in advance, with 34/36 patients enlisted 2 patients were prohibited from this investigation because of unusual standard renal capacity The full information, including creatinine level more than 3 courses of treatment, on 29 patients as of now are accessible. These information were utilized for this measurable investigation

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Methods: Chemotherapy Ifosfamide 2000 mg/m 2 in 500 ml NS more than 2 hr q 12 h x 7 measurements Mesna 400 mg/m 2 blended w. in the first place Ifosfamide measurements Simultaneously, begin mesna 2400 mg/m 2 in 2 liters D 5 w. 150 mEq/l Sodium Acetate + 20 mEq/l K Acetate more than 24 hrs every day x 4 days through pump Dopamine Patients randomized to get or not get dopamine 3mcg/kg/min following 4 hours of IV liquids

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Methods: Chemotherapy IV Fluids D 5 W + 150 mEq/l Sodium Acetate + 4 mEq/l MgSO 4 + 40 mEq/l K Acetate + 20 mEq/l KCl at 125 ml/hr for 4 hr preceding and proceeding with chemotherapy and mesna At finishing of MESNA imbuement, increment IV liquid rate to 250 ml/hr Daily conformity to keep quiet antacid and adjust electrolytes

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Patient Characteristics 29 patients randomized 13 (45%) got dopamine 16 (55%) got no dopamine Age Median 35 years Range 18 - 62 Sex 10 (34%) females 19 (66%) guys

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Statistical Methods Daily creatinine level was measured amid and promptly after ifosfamide more than 3 cycles of treatment, 21 days for every cycle A longitudinal blended impacts straight relapse model was fit, representing : Variation of Creatinine, over the long haul inside cycle Patient Age Baseline Creatinine Treatment (Dopamine versus No Dopamine) Within-Patient Correlation, among the rehashed creatinine estimations

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Predicted Creatinine Levels Over Cycle 1 for a 30-year-old Patient with Baseline Creatinine Level 0.8 Results 95% certainty interims given by vertical lines

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Predicted Creatinine Levels for the Dopamine and No Dopamine Groups by Age (30 versus 52 ) and Baseline Creatinine Level (0.8 versus 1.1 ) in Cycle 1 No Dopamine

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Predicted Creatinine Levels for the Dopamine and No Dopamine Groups by Age (30 versus 52 ) and Baseline Creatinine Level (0.8 versus 1.1 ) in Cycle 2 No Dopamine

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Predicted Creatinine Levels for the Dopamine and No Dopamine Groups by Age (30 versus 52 ) and Baseline Creatinine Level (0.8 versus 1.1 ) in Cycle 3 No Dopamine

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Statistical Results Fitted Linear Mixed Model for Creatinine Levels * A negative sign compares to a lower creatinine level

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Ignoring Baseline Creatinine Accounting for Baseline Creatinine Dopamine No Dopamine No Dopamine P = 0.715 P = 0.014

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Conclusions Dopamine may offer huge assurance from ifosfamide nephrotoxicity The relative greatness of the impact of benchmark creatinine on ensuing creatinine levels is around 10-overlap that of dopamine If we had overlooked gauge creatinine in our model, we would have missed the useful impacts of dopamine

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