Adapted from source


Presentation Objectives
‡ Discuss the emergent management of acute hyperkalemia in unstable adults.
1) Discuss and understand the various tests for hyperkalemia. 2) Discuss and understand the physiology behind the various treatments for hyperkalemia. 3) Discuss the evidence for, and strength of, the various different treatment possibilities for hyperkalemia.


Not Presentation Objectives
‡ This talk is not designed to focus on:
± management of chronic or acute-on-chronic hyperkalemia (in patients with ESRD, patients who are on dialysis, et cetera). ± etiologies of hyperkalemia ± clinical findings in hyperkalemia ± extra-cardiac complications of hyperkalemia ± disposition of hyperkalemic patients


Grab chart and head into patient s cubicle.

First impression
‡ ‡ ‡ ‡ ‡ Mr. S. is lying in a bed. He is a big old man (~112kg, 67yrs). He is moving and looking around. He is very diaphoretic. He looks like hell. What do you want to do now? ABC s and vitals!

‡ Pt is speaking, but responding inappropriately to my questions ‡ Vital signs
± Afebrile, HR 67, RR 24, BP 103/67, 100% on 6L by NP, BSL 6.8

‡ Are you going to call a code, or are you going to keep going for now? Keep going for now. Think about calling a friend.

The EKG and ABG are being done Time for 60 seconds of history. ‡ Pt is BIBA, known case of DM & HTN. ‡ Past history of IHD and AF. ‡ On digoxin, Beta Blocker and on 101 more medications. ‡ Has been non-acute for well over 11 months. ‡ Self-ambulating


‡ ‡ ‡ ‡ ‡ ‡

Normal lung, heart, GI, kidney No PSurghx No allergies Non-smoker, light drinker, no drugs Only close relative is a brother in Sydney No FHx


‡ Unremarkable events at home
± No falls or accidents ± No worrying fluctuations in his behaviour or his LOC ± Gradual history to a state of mild-moderate confusion.

‡ Gets routine follow up once a month with his GP.
± Last B/W was three weeks ago:
‡ Normal CBC/diff ‡ Normal lytes ‡ Normal BUN/Cr

EKG is up«


Junior Doctor s refresher
‡ What are 6 EKG signs of hyperkalemia (in order of increasing severity)?
± ± ± ± ± ±

Peaked T s Shortened QT Lengthened PR QRS widening Flattened P s Sine-wave ( VF/asystole)






Blood gas is up
Less interestingly: 7.42/32/22/100% (on 6L) More interestingly: Na: 137 K: 8.6 HCO3: 20 Cl: 102


So it s the real thing?
‡ Well let s see.
± Pt clinically unwell ± Appropriate EKG manifestations ± Level confirmed by ABG ± This talk is on the treatment of acute hyperkalemia in unstable adults.

‡ So, ehh yeah. It s the real thing.

Why ask if it s real?
‡ Because the #1 cause of hyperkalemia is pseudohyperkalemia, secondary to:
‡ in vitro hemolysis ± small needle ± high-vacuum vacuum tube ± tourniquet use » Labs techs will usually recognize the tell-tale pink serum that accompanies hemolysis, and will report this. ‡ extreme leukocytosis ± K released from WBC s ‡ severe thrombocytosis ± K released from platelets


How should I treat this patient?
‡ Call the medical PHO or ED SMO and let them deal with it.
± Yes this is one option ± But lets put on the big-boy pants for a little while here and pretend that we are the ones who have to save this patient. ± (That being said, getting someone to phone your medical PHO or SMO while you are saving the patient is probably not the worst idea in the world.)


So, how should I treat this patient?
‡ Five general avenues of treatment (you d better get at least four): 1) Stabilize the heart 2) Stop giving K 3) Shift K intracellularly 4) Get the K out of the body 5) Fix the underlying cause We will discuss the first four avenues.

#1- Stabilize the heart


‡ The cardiac sx of hyperkalemia are related to impaired neuromuscular transmission. ‡ The resting membrane potential (rmp) is usually 70mV and (according to the Nernst equation) is governed (in part) by the ratio of intracellular K/extracellular K. ‡ As this ratio drops, the rmp becomes less negative, and depolarization is increased at least, initially.


‡ But persistent depolarization leads to inactivation of the Na channels (which are the main mechanism of neuron depolarization.) ‡ As such, an overall decrease in membrane excitability is manifested ‡ This results clinically in:
± muscle weakness ± decreased reflexes ± impaired cardiac conduction (i.e. bradycardias, widened QRS, etc.)


So how should I stabilize the heart?
‡ No secrets here
± 1 amp (10mL) of 10% Calcium gluconate slow IV push ± contains ~90mg elemental Ca ± Ca has no effect on the overall K level, but it does antagonize the effect of increased extracellular K at the cardiac membrane (by an unknown mechanism). ± As a result, the rmp drops back down to normal, the Na channels are reactivated, and cardiac conduction is restored.


When should I give the Ca?
‡ If possible, wait until after the EKG.
± the EKG offers a secondary method of confirming the high K ± the EKG also offers a gross baseline estimate of cardiac dysfunction
‡ helps one to determine the necessary aggressiveness of treatment ‡ helps one to monitor the response to treatment


That being said
‡ In a patient with a high laboratory K who appears grossly symptomatic and/or unstable ‡ DO NOT WAIT FOR THE EKG! ‡ GIVE THAT CALCIUM!


‡ The protective effect of Ca begins in 1-3 mins, but is relatively short-lived (20-40 mins).
± As such, keep an eye on your EKG monitor while you initiate and continue other treatments. ± Additional doses of Ca gluconate should be given in 5-10 mins (and then q 15-30 mins) if malignant EKG changes persist on the monitor. ± The risk of symptomatic hyperCa is small, but consider re-checking an ABG with lytes if giving >3 doses.



Danger danger.
‡ One possible etiology of hyperkalemia is digitalis toxicity.
± Digitalis work by binding to (and inhibiting) the Na/K pump on cardiac cell membranes. ± As intracellular Na increases, a Na/Ca exchanger attempts to compensate by extruding Na in exchange for Ca. ± The resulting increased sarcoplasmic Ca is thought to be responsible for digitalis increased inotropy.


± The original Na/K exchanger blockade, however, can lead to symptomatic hyperkalemia in digitalis toxicity
‡ But realize that the hyperkalemia here is an effect not the cause of the underlying problem

± As such, giving Ca to fix the hyper-kalemia will only allow even more Ca to enter the cardiac cell (via the Na/Ca exchanger) ± This will worsen the effects of the underlying digitalis toxicity


So don t give Ca if the patient is taking Digoxin? ‡ It s not that simple
± A hyperkalemic patient taking Dig may not be hyperkalemic from the Dig.
‡ You can t wait for a Dig level ‡ Dig levels don t necessarily correspond to dig toxicity in either acute or chronic overdoses ‡ Very few clinical findings will distinguish Dig-based from nonDig-based hyperkalemia
» yellow-green halos


And finally
± Even if the patient is hyperkalemic from his Digoxin toxicity, it is not as though the digitalis toxicity offers a protective effect against the hyperkalemia
‡ i.e. the patient can still die from his hyperkalemia, just as he could die from his digitalis toxicity


So when should I give Ca to a patient taking Dig?
‡ Strong evidence-based guidelines do not exist:
± Kumar & Clark, 3rd Edition
± avoid Ca

± UpToDate
± only given Ca when absolutely necessary » loss of P-waves » QRS-widening


#2 - Stop giving K
‡ Reduce direct sources of potassium ± Replacement K in the IV ± K in NG tube feeds ± K in dialysate ± Potassium supplements (eg. Slow K) ± foods rich in potassium (bananas, oranges, leafy-green vegetables) ± Transfusions of aged-blood ± Medications rich in potassium: ‡ penicillin ‡ carbenicillin


‡ Also consider indirect increasers of K:
± K-sparing diuretics
‡ several different mechanisms

± Beta-blockers
‡ decrease renin release via direct B2-receptor action in the kidney ‡ Therefore, non-selective B-blockers are much more likely to cause hyperkalemia than B1-selective blockers

± ACE-i
‡ decrease the GFR (via effects on AII and the efferent renal vasculature)


‡ decrease the GFR (via effects on prostaglandins and the afferent renal vasculature)

± Succinylcholine
‡ causes transient K efflux secondary to muscle-cell membrane depolarization.

± High-dose TMP-SMX
‡ may be an agent of hyperkalemia in patients with renal insufficiency


#3 Shift K intracellularly
‡ Three main methods available:
1) Insulin +/- glucose 2) Sodium bicarbonate 3) Adrenergic-agonists

‡ Bear in mind
± these are typically temporizing measures
» they are designed to buy you time while you reduce the body s total potassium load


Insulin +/- Glucose
‡ Note that it is the insulin not the glucose which lowers the K.
± The glucose is merely used to increase the body s own insulin secretion.

‡ Insulin drives K intracellularly
± Proposed mechanism:
‡ enhanced Na/K-pump activity in skeletal muscle


How should insulin be dosed?
‡ Several dosing regimens available:
± No one method has been proven to be superior as such always consider your individual patient.
1) 10U regular insulin + 1 amp of D50 (i.e. 50g of 50% dextrose); IV push
(Fast acting insulin is not required you are not attempting to lower sugars.)

2) 1 amp D50 alone; IV push


± the insulin+glucose regimen may be more effective than glucose alone in reducing potassium. ± the glucose-alone regimen does not carry the risk of hypoglycemia present with the insulin+glucose regimen. ± both treatments will generally cause a drop in K of 0.5 to 1.5 meq/L ± this effect will usually take 15-30mins to begin, will peak at ~1hr, and will last for 4-6hrs.


‡ A 10U dose of regular insulin will induce a significant drop in glucose in most patients unless adequate glucose is also given up front
± i.e. if given with an amp of D25 (as opposed to an amp of D50), 10U of regular insulin will cause sugars to fall below 3mmol/L in up to 75% of initially normoglycemic patients

‡ Therefore, monitor BSL closely when treating hyperkalemia pts with insulin:
‡ eg. 30mins, 60mins, 120mins


Quick word on diabetics
‡ Insulin is still effective at activating the Na/K pump in diabetics (i.e. in reducing K) even in patients who are resistant to insulin s glycemic effects. ‡ Regimens:
± if patient is hyperglycemic, give insulin alone. ± if patient is normoglycemic, give insulin+glucose.


Sodium Bicarbonate
‡ Proposed mechanism:
± Raising the serum pH with NaHCO3 results in the release of H+ from cells (buffering action). ± This increase in H+, (in order to maintain electroneutrality) drives K+ intracellularly ± In addition, HCO3 also appears to directly reduce serum K+ by an unknown but pH-independent method.


‡ As monotherapy, NaHCO3 tends to be:
± more effective in:
» pts with a metabolic acidosis accompanying the hyperkalemia (does this make sense?)

± less effective in:
» pts with advanced renal failure


NaHCO3 Dosing
‡ No strong evidence exists as to the optimal dosing amount or strategy:
± As such, the following strategy is suggested as one that is both simple and fast. ‡ 1-2 amps (50-100meq) of NaHCO3; given one after another, both via a slow IV push ‡ a 3rd amp may be given in 30 mins if pt remains dangerously hyperkalemic

‡ Bicarb will begin to work in 5-10mins, and will continue to work for 1-2hrs

‡ Mechanism
± The B-agonists work in the same manner as insulin by increasing Na/K pump activity

‡ B-agonists that can be used include:
± Ventolin
‡ can be given via Neb or intravenously

± Epinephrine
‡ can be given via a slow IV infusion ‡ (less commonly used than Ventolin for both logistical and medical reasons.)


‡ Ventolin
± Nebulizer: » 10-20mg (large dose) given over 10mins » begins to work in 15-30mins, peak effect in 90mins, lasts 3-4hrs ± IV: » 0.5mg IV given over 10mins » begins to work in minutes, peak effect in 30mins ± Both regimens will cause a drop in plasma K of 0.5-1.5 meq/L, but IV ventolin works faster ± The nebulized route, however, might be easier to initiate in a hurry.

‡ B-agonist use is obviously less advisable in patients with heart disease.
‡ most typical side effect would be a mild tachycardia ‡ that being said, one could potentially induce angina in patients with coronary disease
» especially if using Epinephrine


#4 Get K out of the body
‡ Once again, three main methods:
1) 2) 3) Cation-exchange resins Diuretics Hemodialysis


Cation-Exchange Resins
‡ The most commonly used cation-exchange resin is Kayexalate (sodium polystyrene sulfonate). ‡ Kayexalate draws potassium into the GI tract (in exchange for sodium) via Na/K pump in the gut lumen.
± Its primary site of action is in the large intestine

‡ Once drawn into the gut, K is bound to the resin and excreted in the feces.


‡ Each gram of resin binds ~ 1meq of K in exchange for ~2-3 meq of Na.
± In patients with CHF, this large sodium load can lead to problems with symptomatic fluid overload.

‡ In the process of removing K from the body, significant amounts of Ca and Mg also tend to be removed.
± As such, it requires an astute physician to closely monitor these secondary (as well as the primary) electrolytes following cation-exchange-resin administration.


‡ Oral dosing
± 25g of Kayexalate PO or NG ± begins to work in ~2hours, can be repeated every 46hrs as necessary

‡ Rectal dosing
± 50g of Kayexalate as a retention enema ± must be retained for at least 30mins, and preferably for up to 6 hours!! ± Begins to work in ~30mins, and can be repeated every 2-4hrs as necessary

‡ Either method can reduce serum K by 0.5-1 meq/L.


‡ As mentioned, resins can cause:
± hypernatremia ( fluid overload) ± hypocalcemia ± hypomagnesemia

‡ The resins also tend to be dramatically constipating, and should be given with a laxative such as sorbitol or lactulose
± Actual Kayexalate -brand cation-binding resin is already mixed in sorbitol and requires no further laxative to be added.

‡ The most serious possible adverse effect of cationexchange resin administration is the possibility of bowel necrosis.
± this risk is typically very small (<1%), but may be as high as 1% when given with sorbitol during the first week after bowel surgery » reduced colonic motility increases resin contact with the mucosa. » sorbitol may directly damage the gut mucosa. ± if a resin must be administered in this setting, cleansing enemas pre- and post- resin administration may prevent excessive drug retention in the gut lumen.




‡ K+ absorption in the kidney takes place in the PCT and the loop of Henle.
± Therefore, by the end of the loop of Henle, all K resorption that is going to take place, has taken place.

‡ In acute hyperkalemia, two types of diuretics are commonly used to induce a K-wasting:
» Thiazide-type diuretics » Loop diuretics


Thiazide-type diuretics
‡ Thiazides act at the loop of Henle and at the DCT, by blocking the Cl portion of the Na/Cl symport. This prevents Na and Cl from entering the tubule, which in turn induces a Na and Cl diuresis.



‡ Thiazides cause K+ loss by two main mechanisms:
1)The induced Na loss will stimulate aldosterone production (in an attempt to conserve Na in the DCT and the collecting tubules). -As such, Na will be retained in exchange for K in these areas. 2)Loss of Cl will result a hypochloremic alkalosis. -The kidney will attempt to compensate by retaining H+ and Clin exchange for potassium.


Loop diuretics
‡ Loop diuretics act similarly to thiazide diuretics, but are specific for the Na/K/Cl symport in the loop of Henle (not just the Na/Cl symport). ‡ These also act by binding to the Cl site, and block tubule resorption of all three ions (Na, K, & Cl). ‡ Loop diuretics therefore produce a more profound K-loss than thiazides.
± Directly block K resorption in addition to inducing the subsequent K losses that result as the body attempts to conserve Na and Cl (as previously discussed).

‡ Since loop diuretics act faster and produce a more profound K loss than thiazide-type diuretics, they tend to be the diuretics of choice in acute hyperkalemic crises.
± Lasix 40-80mg IV push


‡ Hemodialysis corrects hyperkalemia rapidly and effectively. ± starts to work in minutes and can remove 25-50 meq of K per hour ± removes K from the body many times faster than peritoneal dialysis ‡ May represent the only feasible option for hyperkalemia Rx in several settings: ± when conservative Rx has failed, or is not working rapidly enough ± in pt s with ESRD (in whom many of the conservative Rx s are less effective) ± when the hyperkalemia is the result of severe rhabdomyolysis

‡ Emergent dialysis for acute hyper-kalemia will obviously have to be arranged in consultation with Nephrology +/- the ICU.
± They may choose to lower the K with a dialysate bath ranging anywhere from 0 to 4 meq/L ± lower-K baths will remove K more rapidly but increase the chance of cardiac dysrhythmias and accidental hypokalemia.


That s pretty much it.
So one example of a typical treatment regimen for severe acute hyperK might be:
‡ ‡ ‡ ‡ ‡ ‡ ‡ ‡

Ca gluconate (if no contraindications) Stopping all extraneous K sources Insulin+glucose NaHCO3 Ventolin nebs Kayexalate retention enema IV Lasix Nephro/ICU consult for possible dialysis


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