Acute treatment of hyperkalemia in patients with end-stage renal disease requires temporizing measures to shift potassium rapidly from the extracellular to the intracellular fluid compartments until hemodialysis can be initiated. Whereas insulin and albuterol are effective in lowering plasma potassium acutely, bicarbonate by itself is not. Bicarbonate administration may, however, potentiate the effects of insulin and albuterol on plasma potassium. Using a prospective cross-over design, we investigated the acute effects of (1) isotonic bicarbonate, (2) isotonic saline, (3) insulin + bicarbonate, (4) insulin + saline, (5) albuterol + bicarbonate, and (6) albuterol + saline on plasma potassium as well as blood bicarbonate and pH in nondiabetic hemodialysis patients. After obtaining a baseline blood sample, the subjects received one of the six treatment protocols, with plasma potassium measured every 15 minutes over 1 hour. Neither isotonic bicarbonate nor isotonic saline decreased plasma potassium significantly (-0.03 +/- 0.06 mmol/L v -0.01 +/- 0.10 mmol/L at 60 minutes; P = 0.60). Intravenous insulin decreased plasma potassium by a similar degree when given in conjunction with bicarbonate or saline (-0.81 +/- 0.05 mmol/L v -0.85 +/- 0.06 mmol/L at 60 minutes; P = 0.65). Likewise, nebulized albuterol decreased plasma potassium by a similar degree when given with bicarbonate or saline (-0.71 +/- 0.16 mmol/L v -0.53 +/- 0.15 mmol/L at 60 minutes; P = 0.18). The three protocols that included bicarbonate administration resulted in significant increases in blood bicarbonate (P < 0.005) and pH (P < 0.01), whereas the three protocols that included saline did not affect blood bicarbonate or pH. These observations suggest that bicarbonate administration does not potentiate the potassium-lowering effects of insulin or albuterol in hemodialysis patients.