The management of hyperkalemia in an acute care setting seems pretty straight forward. Force potassium intracellularly with insulin, while potassium binders assist with actual excretion of the electrolyte. However, there are some caveats to know about this age-old strategy, and why it is effective.
CALCIUM GLUCONATE – We all know how the old adage goes: Give calcium gluconate first in a hyperkalemic patient to “stabilize the cardiac membrane.” While this explanation is generally good enough in a pinch, WHY does it stabilize the cardiac membrane? Well, in an environment with normal levels of potassium, the resting membrane potential is about -90mV, while the threshold for an action potential is -70mV. In a hyperkalemic environment, this resting potential actually increases to -80mV, making it easier to reach the threshold. The resting potential also determines how many sodium channels open during phase 0, with less being opened at -80mV than -90mV. This leads to initial tachyarrhythmias with a widened QRS, such as ventricular tachycardia.
Calcium works to restore the resting potential using it’s 2+ positive charge, making it closer to -90mV. Calcium also has an impact on the number of sodium channels that open. There are calcium-binding receptors that have downstream effects which increase the number of activated sodium channels.
In essence, calcium does “stabilize the cardiac membrane” by counteracting the overexcitability of an increased resting potential AND restores balance to phase 0 and the number of activated sodium channels. One caveat to treatment with calcium is that the calcium will redistribute, so it only has an effect for approximately 30-60 minutes.
INSULIN/DEXTROSE – Insulin works as a temporizing measure to force potassium from the extracellular space (like plasma/blood) to the intracellular space, such that it can’t produce cardiotoxic effects. Insulin agonizes the Na-K-ATPase pump, which allows sodium out of the cell in exchange for pumping potassium into the cell. Dextrose is solely given to avoid hypoglycemia, assuming the patient’s glucose isn’t already sky-high.
Effects on serum potassium levels begin in 10-20mins, peaking in 60mins, and lasting anywhere from 2-6 hours at a standard dose of 10 units of regular insulin given IV.
One caveat to this regimen is that many clinicians will just administer the insulin and dextrose and call it a day, but the hypoglycemic effects of the insulin can persist for up to 6 hours. So, it’s very important to continue to check blood glucose levels so our patients don’t become hypoglycemic!
POTASSIUM BINDERS – In patients where it is feasible and reasonable, the oral potassium binding agents are the true workhorses of the regimen, forcing potassium to actually be excreted from the body. Though SPS (Sodium polystyrene sulfonate/Kayexalate) has largely fallen out of favor due to risks of colonic necrosis, two other potassium binders come to mind: Sodium zirconium cyclosilicate (Lokelma) and Patiromer (Veltassa). Both of these are non-absorbed potassium binders that exchange other molecules or cations for potassium in the GI tract, leading to potassium being trapped in the polymer and excreted through normal GI means.
One difference that is notable between the two of them is that Lokelma has an onset of action of 1 hour, while Veltassa may take up to 7 hours to work. The trade off is that Lokelma has about 400mg of Sodium per 5g of drug (usual dose is 10g) so edema may be more common, and you may want to use veltassa in heart failure/fluid overload-prone patients instead.
BETA AGONISTS – Albuterol. Activates Na-K-ATPase pumps additively to insulin, so it is also useful for acutely pushing potassium intracellularly if needed, at a nebulized dose of 10-20mg. Albuterol has a rapid onset of about 5mins, and effects persist for 1-4 hours.
One caveat to this idea is that patients on beta blockers are unlikely to respond for obvious reasons. Our institution tends to reserve using albuterol in hyperkalemic patients for only those with definitive EKG changes, like peaked T-waves.
LOOP DIURETICS – Promote renal excretion of potassium in about 5-30mins, persisting for 2-6 hours! Just make sure you give fluids to promote more excretion and intravascular dilution in patients who aren’t volume overloaded. Also my advice about sulfa allergies: Cross-allergenicity is limited to case reports! CASE REPORTS!!
SODIUM BICARBONATE – FALSE, no proven benefit, may cause hypernatremia, metabolic alkalosis, and fluid overload. Moving on!
HEMODIALYSIS – Definitive and immediate management of hyperkalemia, if you are able to do so and the patient is stable enough. I don’t think further explanation is really warranted here, the diffusion across a membrane speaks for itself.
I hope this little guide on hyperkalemia provides some clarification as to why certain things work the way they do, as well as some side effects/onset times/monitoring parameters to look out for the next time you are managing a hyperkalemic patient!