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Reported associations between weight and amplitude of QRS complexes in patients with anasarca and those undergoing hemodialysis (HD) led to the hypothesis that similar alterations in the P waves may occur with changing edematous states. The objective of this study was to explore whether anasarca or the state prior to HD are associated with attenuated P waves. The sum of P wave amplitude in millimeters measured in the 12 leads of the ECG (ΣP) was calculated in 28 patients with anasarca, 28 “controls,” without change in their weight during hospitalization, and in 1 patient before and after 26 HD sessions. Admission ΣP (10.5 ± 4.9 mm) decreased at peak weight (3.8 ± 2.0 mm, P = 0.0005) in patients with anasarca and increased at subsequent lowest weight in those who lost weight (2.3 ± 1.3 vs 6.15 ± 1.6 mm, P = 0.002). Admission and discharge ΣPs were 10.9 ± 4.5 and 9.8 ± 3.8 mm, P = 0.062 in the controls, and 13.7 ± 2.8 mm before and 18.2 ± 3.0 mm after HD, P = 0.0005. In the patients with anasarca, the percent of decrease in ΣP correlated well with the percent of increase in weight (r = 0.70, P = 0.0028) and percent of decrease in the sum of QRS complexes from all 12 ECG leads (r = 0.62, P = 0.01). After HD, the percent of increase in ΣP correlated with percent of increase in the body electrical resistance (r = 0.44, P = 0.029), reactance (r = 0.46, P = 0.020), and impedance (r = 0.44, P = 0.029). Alterations in P wave amplitudes, commensurate with the ones affecting the corresponding QRS complexes, occur in patients developing anasarca, and those undergoing HD. This observation suggests that accurate measurement of the P wave amplitudes in such patients cannot be made until the fluid overload is alleviated, and this factor should be taken into consideration when repeat P wave measurements are compared.