A recent renal consult I encountered was a Cantonese gentleman with a classical symptomatic history for Hypokalemic Periodic Paralysis (HPP). He presented with a serum K of 1.4 mmol/l and profound weakness. Initially beginning in his teenage years, he had intermittent attacks of weakness lasting hours and affecting proximal muscle groups. Emergency department admissions invariably revealed low serum K.
Many of us will know the classical features to look for in the history:
- High risk Asian and Hispanic population groups, particularly males less than 20 years old.
- High carbohydrate meals triggering insulin release or B-adrenergic surge from exercise or volume depletion.
- Thyrotoxicosis: A major subgroup of patients, usually men. The mechanism is thought to involve a combination of up regulation of Na-K-ATPase, loss of function of the inward potassium rectifying channel Kir2.6, and a feed forward effect in certain variants of the sulphonylurea receptor 1, culminating in dramatic intracellular potassium shifts. It is important to note is that rarely the paralytic episodes can predate the thyroid disease by many years.
The genetics of hypokalemic periodic paralysis have been discussed previously on Renal Fellow Network.
Management: More Questions than Answers
Acute management is relativity straightforward – administration of K, either IV or orally. Case control series demonstrate up to 70% of patients having rebound hyperkalemia of >5mmol/l if KCl doses of over 90mmol/ are administered. Lower doses may potentially be used if concomitant B-blockade is deployed in conjunction. Oral KCl rescue is more suitable for home use. As a rule of thumb, 40 to 60 mmol/l of oral K+ raises plasma potassium concentration by 1.0 to 1.5 mmol/L, and 135 to 160 mmol/l K+ raises plasma potassium by 2.5 to 3.5 mmol/l.
Besides avoiding obvious environmental triggers, therapeutic interventions and prophylaxis are more unclear. Patients have normal total body potassium with no chronic GI or renal loss, thus the drop in serum levels is mediated via a transcellular shift. Despite this, prophylactic K supplementation remains a traditional cornerstone of therapy, although one would imagine a normally functioning cortical collecting duct should excrete this quite rapidly, particularly with chronic dosing regimens.
The “highest quality” of evidence comes from a Cochrane review of 3 very small studies, the largest examining the utility of dichlorphenamide, a carbonic anhydrase inhibitor, in 34 patients. Self-reported quality of life improved in 15 patients, and attack frequency dropped. This is in line with a more recent study in 2011 which quote a 50% improvement in symptoms in a larger group of patients on dichlorphenamide. This is unusual as the additional HCO3 in the collecting duct should increase intraluminal negative charge, and encourage potassium excretion, as should the volume depletion and increased RAAS activity. Furthermore, volume depletion could theoretically induce increase sympathetic output, worsening K loss. The most plausible explanation I found was a paper from 1975 suggesting the metabolic acidosis induced by the carbonic anhydrase inhibitor buffers the transcellular shift of K+.
Despite aldosterone levels being normal during attacks, reports suggest aldosterone antagonists may benefit patients as a second line therapy via their K+ retaining effects, although their action appears to be opposite to that of dichlorphenamide. It is curious these agents with supposed diametric effects on renal K handling both have positive effects on K balance in HPP.
The most intuitive treatment is B-blockade, demonstrated in a number of series to be effective, but almost always in those whose HPP occurs in association with thyrotoxicosis.
Authored by Eoin O'Sullivan