Problem 1: Too much insulin

Insulin is given to patients with abnormally elevated potassium. It works by upregulating the Na-K ATPase pump, so that potassium is moved intracellularly. As a rough guide, the standard dose of 10 units will lower serum potassium by around 1mmol/L. It'll take around 20min to do this and the effect will last for around 4 hours.^​[1]​

Unfortunately, this therapy carries a significant risk of hypoglycaemia even if the insulin is given with IV dextrose, as is common practice. Two studies from 2019 demonstrated an incidence of hypoglycaemia of around 20%.^​[2,3]​

Today's paper is interesting because it attempts to quantify this drop in blood glucose, or [BG].

The paper

Aljabri A, Perona S, Alshibani M, et al. Blood glucose reduction in patients treated with insulin and dextrose for hyperkalaemia. Emerg Med J. 2020;37(1):31-35^​[4]​

A multi-centre retrospective cohort study of 90 patients with hyperkalaemia. Each received 10 units of IV insulin plus 25g of IV dextrose (equivalent to 50ml of 50% solution). The authors measured the effect of this treatment on [BG]. Here are the results...

The authors found there was a transient increase in [BG] during the first hour, but this was followed by a reduction in subsequent hours. They suggest that the initial protective effects of dextrose are 'outlived' by the exogenous insulin, or overcome by endogenous insulin production in response to the increased [BG].

So what is the solution to this problem? Well, we could half the dose of insulin. A 2017 paper^​[5]​ found this reduced the incidence of hypoglycaemia but didn't affect the reduction in potassium (see our summary here). Another option would be to 'preload' your patient with dextrose before starting insulin if their initial [BG] was low.

Take home points

1. Treating hyperkalaemia with insulin will cause blood glucose levels to fall, even if you co-administer dextrose

2. The drop in blood glucose is highly variable, but may be as much as 2.9mmol/L (53mg/dL)

3. The effects of IV dextrose will wear off before those of insulin, so check blood glucose after 1-2 hours

Problem 2: Too little calcium

Hyperkalaemia reduces the resting membrane potential of cardiac myocytes, so they are more likely to spontaneously depolarise. This can result in arrhythmias, of which VF and subsequent cardiac arrest are the worst outcomes. Additionally, hyperkalaemia doesn't usually cause any symptoms - this combination of features make it particularly dangerous. Thus the saying...

"The first symptom of hyperkalaemia is death."^​[6]​

Calcium antagonises this effect of potassium on the cardiac myocytes, stabilising the membranes and reducing the risk of arrhythmias. No one really doubts the physiology behind this therapy, but it might surprise you to learn that there have never been RCTs to confirm its efficacy. Additionally, there is apparently no consensus on when calcium should be given and what the best dose is. Thankfully, we have some very sensible advice from the UK Renal Association.^​[7]​ Still, in my experience their recommendations are not widely known.

Before we get to it, and in case you think I'm being a bit of a cowboy with what follows, it's worth bearing in mind that the document was written by...

• 4 consultant nephrologists


• 3 consultant anaesthetists


• 1 consultant in acute medicine

And it was fully endorsed by...

• The UK Resuscitation Council


• The Intensive Care Society


• The Faculty of Intensive Care Medicine


• The Society for Acute Medicine


• The College of Emergency Medicine (we weren't 'Royal' back in 2014!)

Are you ready for this?

Firstly, 10ml of 10% calcium gluconate contains 2.26mmol of ionised calcium. 10ml of 10% calcium chloride contains 6.8mmol. The reason calcium gluconate is preferred in most cases is that there is a risk of tissue necrosis if extravasation occurs, and this preparation is more dilute. The authors recommend that an equivalent dose is given in high-risk hyperkalaemia (i.e. 6.8mmol, which is 30ml of 10% calcium gluconate).

Secondly, potential adverse effects of calcium include peripheral vasodilation, bradycardia, hypotension, syncope and arrhythmias. Each of these is quite rare, but the risk is not zero. Therefore, the authors recommend that calcium be reserved for those patients who actually need it - those with ECG evidence of cardiac membrane instability. These would include peaked T waves, prolonged PR interval, flattened P waves, widened QRS complexes, brady- and tachycardias.

Thirdly, IV calcium has a relatively short duration of action. In cases of prolonged hyperkalaemia, the ECG should be continuously monitored and we should be ready to repeat the calcium dose in 30-60 minutes if needed.

Take home points

1. Use 10% calcium gluconate unless you have a central line. Give 3 sequential doses of 10ml until the ECG normalises

2. Only give calcium if there are ECG changes associated with hyperkalaemia

3. The duration of action is 30-60min, so be ready to repeat the dose if ECG changes reappear

References

1. 
   
   
   

   Li T, Vijayan A. Insulin for the treatment of hyperkalemia: a double-edged sword? Clin Kidney J [Internet] 2014;7(3):239–41. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25852882

   
   
   
   


2. 
   
   
   

   Jacob B, Peasah S, Chan H, Niculas D, Shogbon N. Hypoglycemia Associated With Insulin Use During Treatment of Hyperkalemia Among Emergency Department Patients. Hosp Pharm [Internet] 2019;54(3):197–202. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31205332

   
   
   
   


3. 
   
   
   

   Scott NL, Klein LR, Cales E, Driver BE. Hypoglycemia as a complication of intravenous insulin to treat hyperkalemia in the emergency department. The American Journal of Emergency Medicine [Internet] 2019;209–13. Available from: http://dx.doi.org/10.1016/j.ajem.2018.05.016

   
   
   
   


4. 
   
   
   

   Aljabri A, Perona S, Alshibani M, Khobrani M, Jarrell D, Patanwala A. Blood glucose reduction in patients treated with insulin and dextrose for hyperkalaemia. Emerg Med J [Internet] 2020;37(1):31–5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31653693

   
   
   
   


5. 
   
   
   

   LaRue H, Peksa G, Shah S. A Comparison of Insulin Doses for the Treatment of Hyperkalemia in Patients with Renal Insufficiency. Pharmacotherapy [Internet] 2017;37(12):1516–22. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28976587

   
   
   
   


6. 
   
   
   

   Glasziou P. Practice corner: the first symptom of hyperkalemia is death. ACP J Club [Internet] 2004;140(2):A13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15122875

   
   
   
   


7. 
   
   
   

   Alfonzo A. Clinical Practice Guideline: Treatment of Acute Hyperkalaemia in Adults [Internet]. UK Renal Association2014 [cited 2020 Jan];Available from: https://renal.org/guidelines/