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]