Redistribution of potassium
Insulin-glucose
Insulin temporarily reverses hyperkalemia by shifting sodium out of the cell in exchange for potassium via the activation of sodium–potassium ATPase pump. Bolus insulin is recommended to be administered as 10 units of regular insulin intravenously given along with an intravenous bolus of dextrose 25-50 g. This regimen when given to anephric adult patients resulted in a reduction of serum potassium concentrations by about 0.6 mmol/L in <15 minutes. This effect can last between 30 and 60 minutes after a single bolus followed by a gradual serum potassium rebound. [31 32] Caution should be used when administering IV insulin to patients with kidney dysfunction, as insulin is renally eliminated. Hypoglycemia can occur for up to 6 hours after IV insulin administration, therefore frequent blood glucose monitoring is advised for the first 4-6 hours after administration. [33 34] The sensitivity to insulin varies with diabetes severity and current renal function. A prospective observational study of 72% of patients with CKD found that 17% of patients who received insulin-glucose therapy developed symptomatic hypoglycemia. [33] Various studies have explored different insulin dosing strategies in the setting of renal dysfunction. LaRue et al [34] and Pierce et al [35] found that patients with kidney failure who received 10 or 5 units of regular insulin achieved similar rates of serum potassium reduction and hypoglycemia. Conversely, one study reported that an insulin dose of 5 units significantly reduced the risk of hypoglycemia compared with 10 units, with an increase in serum creatinine being associated with an increased risk for hypoglycemia. [36] Farina et al [37] concluded that the use of 50 g of dextrose instead of 25 g did not reduce hypoglycemia incidence. It should be noted that the evidence is limited by small cohort sizes and retrospective design. The KDIGO guidelines recommend the administration of 5 units regular insulin along with 25g of dextrose in patients with CKD. [23]
Beta-2 Agonists
Beta-2 adrenergic receptor agonists work by promoting the activation of sodium–potassium ATPase pumps resulting in intracellular potassium shifting.[38] Salbutamol, intravenously or by nebulization, has been shown to be an effective agent in treating hyperkalemia. The nebulized route is preferred due to the ease of administration and fewer side-effects. [39-41] With a dose dependent effect, the onset of action of salbutamol is 30 minutes with a peak effect within 60 minutes.[42] It reduced serum potassium levels by approximately 1 mmol/L, and the effect persisted for at least 2 hours. Salbutamol via nebulizer can be given in doses of 10 or 20 mg.[32 43 44]. Albuterol is another beta-2 agonist commonly used in the treatment of hyperkalemia in the United States (US). When albuterol was given as 10 mg nebulization, the serum potassium concentration was lowered by a mean of 0.62 mmol/L, and 20 mg reduced serum potassium by 0.98 mmol/L after 2 hours. [42] Administration of these relatively high doses of beta-2 agonists may lead to tremor, tachycardia, and headache. In KT recipients on tacrolimus, tremors and headaches caused by beta-2 agonists can be confused with tacrolimus toxicity.
Sodium bicarbonate
By raising extracellular bicarbonate levels, an increase in sodium–potassium ATPase pump activity results in an increase in uptake of intracellular potassium. [10] The use of bicarbonate infusion fails to lower serum potassium acutely and therefore has fallen out of favor.[43 45] However, in a case series of patients with metabolic acidosis (pH < 7.35), a decrease in serum potassium concentration (1.5–3.0 mmol/L) in response to sodium bicarbonate was observed. [46-48] Sodium bicarbonate should be avoided in hypervolemic patients due to the risk of sodium overload and pulmonary edema. [49 50] In general, oral sodium bicarbonate (3-5g/day) should not be used as a first line treatment, and should be considered only in patients with concomitant metabolic acidosis (HCO3 < 22mmol/L). However, it appears less effective in lower serum potassium levels in patients with advanced CKD [23 51]