ACADEMIC EMERGENCY MEDICINE • September 2000, Volume 7, Number 9 965 BASIC INVESTIGATIONS Hypertonic Saline Treatment of Severe Hyperkalemia in Nonnephrectomized Dogs JUSTIN L. KAPLAN, MD, C. ANDREW EYNON, MBBS, WILLIAM C. DALSEY, MD, MBA, LEONARD E. BRAITMAN,PHD, DAWN CLAS,LAWRENCE DE GARAVILLA,PHD Abstract. Objectives: To determine whether a hy- pertonic saline bolus improves cardiac conduction or plasma potassium levels more than normal saline in- fusion within 15 minutes of treatment for severe hyperkalemia. Previously with this model, 8.4% so- dium chloride (NaCl) and 8.4% sodium bicarbonate (NaHCO 3 ) lowered plasma potassium equally effec- tively. Methods: This was a crossover study using ten conditioned dogs (14–20 kg) that received, in random order, each of three intravenous (IV) treatments in separate experiments at least one week apart: 1) 2 mmol/kg of 8.4% NaCl over 5 minutes (bolus); 2) 2 mmol/kg of 0.9% NaCl over one hour (infusion); or 3) no treatment (control). Using isoflurane anesthesia and ventilation (pCO 2 = 35–40 torr), 2 mmol/kg/hr of IV potassium chloride (KCl) was infused until con- duction delays (both absent p-waves and $20% de- crease in ventricular rate in #5 minutes) were sus- tained for 15 minutes. The KCl was then decreased to 1 mmol/kg/hr (maintenance) for 2 hours and 45 minutes. Treatment (0 minutes) began after 45 minutes of maintenance KCl. Results: From 0 to 15 minutes, mean heart rate increased 29.6 (95% CI = 12.2 to 46; p < 0.005) beats/min more with bolus than infusion and 23.4 (95% CI = 2.6 to 43.5; p < 0.03) beats/min more with bolus than control. No clinically or statistically significant difference was seen in heart rate changes from 0 to 30 minutes. Decreases in potassium from 0 to 15 minutes were similar with bolus, infusion, and control. Conclusions: In this model, 8.4% NaCl bolus reversed cardiac conduction abnormalities within the first 15 minutes after treat- ment, more rapidly than did the 0.9% NaCl infusion or control. This reversal occurred despite similar re- ductions in potassium levels. Key words: hypertonic; sodium; hyperkalemia; treatment; animal model. AC- ADEMIC EMERGENCY MEDICINE 2000; 7:965– 973 T HERE is controversy regarding the use of so- dium bicarbonate (NaHCO 3 ) in the emer- gency treatment of hyperkalemia. Despite the fact that alkalinization is often taught to be the stan- dard of care, 1,2 most investigations have shown lit- tle or no benefit to alkalinization for emergent (i.e., benefits within 15–60 minutes of treatment) treat- ment of hyperkalemia. 3–6 From the Department of Emergency Medicine (JLK, CAE, WCD, DC, LdG) and the Office for Research and Technology Development (LEB), Albert Einstein Medical Center, Philadel- phia, PA; the Department of Internal Medicine, Temple Uni- versity Health Sciences Center, Philadelphia, PA (JLK, WCD); GDL Consulting, Downington, PA (LdG); and Cephalon, Inc., West Chester, PA (DC). Received October 1, 1999; revisions received January 18, 2000, March 8, 2000, and April 10, 2000; accepted April 21, 2000. Presented at the SAEM annual meeting, Washington, DC, May 1997. Address for correspondence and reprints: Justin L. Kaplan, MD, Department of Emergency Medicine, Albert Einstein Med- ical Center, 5501 Old York Road, Philadelphia, PA19141. Fax: 215-456-8502; e-mail: kaplanj@aehn2.einstein.edu Sodium bicarbonate may decrease potassium in hyperkalemia by sodium loading rather than by al- kalinization. Janson and Marx speculated that in- fusion of sodium solutions may be effective in hy- perkalemia. 7 A recent animal study, using a crossover design in dogs given potassium loads (mean 6 SD pretreatment potassium level of 9.06 6 0.82 mmol/L), compared various treatments matched in sodium and water content. 8 A bolus of 8.4% sodium chloride (NaCl) (2 mmol Na/kg) caused potassium to decrease at least as much as a bolus of 8.4% NaHCO 3 (2 mmol Na/kg). Reduc- tion of potassium levels by the concentrated so- dium solutions from a mechanism other than alkalinization (for example, hemodilution, ion dis- placement, or some other mechanism) could not be ruled out. No difference was seen in cardiac con- duction between the treatments. Determining the efficacy of hypertonic sodium solutions for hyperkalemia is important clinically. These solutions should not be used unless effica- cious since they are potentially harmful. For ex-