Date post: | 14-Apr-2017 |
Category: |
Documents |
Upload: | steve-chen |
View: | 152 times |
Download: | 4 times |
A New Perspective on Hyperkalemia
Taipei Veterans General Hospital, Hsin-Chu branch
Director of Nephrology
Steve Chen
K
PotassiumPotassium
Reference Range:3.5 – 5.1 meq/L
PotassiumPotassium
Hyperkalemia is K+ > 5.5 meq/L
Pseudohyperkalemia Pseudohyperkalemia Poor phlebotomy technique:
fist clenching during phlebotomy raises both serum and plasma potassium by as much as 1 meq/L
Hemolysis : improper drawing blood Thrombocytosis ( > 500,000/µl)
Potassium is released from platelets during clotting, raising the serum but not plasma potassium platelet-induced serum pseudohyperkalemia
Leukocytosis Leukemic lymphocytes are fragile and release potassium during centrifugation when exposed to high concentrations of heparin in the test tube ( reverse pseudohyperkalemia ) lymphocyte-induced plasma pseudohyperkalemia
Definitions of the severity of Definitions of the severity of hyperkalemiahyperkalemia
Author Year Mild Moderate Severe
Levinsky 1966 < 6.5 mmol/l
6.5–8 mmol/l with ECG : peaked T-waves
>8 mmol/l or any level + prolongation of the QRS complex/ventricular arrhythmias/heart block
Vanden Hoek et al.for American Heart Association
2005 5.1–5.9 mmol/l
6.0–6.9 mmol/l >7 mmol/l
Soar et al.for the European Resuscitation Council
2010 5.5–5.9 mmol/l
6.0–6.4 mmol/l ≥6.5 mmol/l
El-Sherif and Turitto
2011 5.5–7.5 mmol/l
7.5–10 mmol/l >10 mmol/l
Symptoms & Signs of Symptoms & Signs of Hyperkalemia Hyperkalemia
Clinical FeaturesClinical Features– CardiovascularCardiovascular
V-Fib, complete heart block, asystoleV-Fib, complete heart block, asystole EKG abnormalitiesEKG abnormalities
– Tall, peaked T-waves, short QT, prolonged PRTall, peaked T-waves, short QT, prolonged PR– QRS widening, flattening of P-waveQRS widening, flattening of P-wave– QRS complex degrades into sine wave patternQRS complex degrades into sine wave pattern
EKG findingsEKG findings Increased T-wave amplitude 6 to 7 meq/L
Prolonged PR interval
QRS widening 7 to 8 meq/L Loss of P wave
Sine wave pattern 8 to 9 meq/L
Ventricular fibrillation or a-systole > 9meq/L
EKGEKG
Symptoms & Signs of Symptoms & Signs of HyperkalemiaHyperkalemia
Clinical Features (Cont)Clinical Features (Cont)– NeuromuscularNeuromuscular
Weakness, paresthesiasWeakness, paresthesias Areflexia, ascending paralysisAreflexia, ascending paralysis
– GastrointestinalGastrointestinal Intestinal colicIntestinal colic DiarrheaDiarrhea
Hyperkalemia, extra-renalHyperkalemia, extra-renal
UK secretion > 200meq/DGI: only if UK excretion↓Redistribution:
Metabolic acidosis: nonorganic Hormones: insulin deficiency, β-blockers Necrosis or depolarization Hyperkalemic periodic paralysis
Trans-cellular shiftTrans-cellular shift
Hyperkalemia, renalHyperkalemia, renal Expected renal response:
UK excretion > 200meq/D; TTKG > 10 UK excretion < 200meq/D Renal
CCr < 25ml/min ↓ GFR CCr > 25ml/min ↓ Tubular secretion
Low flow rate in CCD if TTKG > 10: low osmoles or flow confirm with loop diuretic
Low K in secretion in CCD if TTKG < 5: aldosterone minus check response to 9αF
Trans-tubular K GradientTrans-tubular K Gradient
TTKG: to interpret urine K by adjusting ﹝ ﹞it for water reabsorption in renal medulla to reflect K in lumen of CCD﹝ ﹞
TTKG= Uk÷(Uosm/Posm) /Pk﹛ ﹜TTKG, physiological : 6 ~ 8
Hyperkalemia, tubular secretion Hyperkalemia, tubular secretion TTKG < 5 TTKG > 10 Decreased circulating volume
Response to Low protein diet 9a-fludrocortisone
TTKG >10 TTK<10 Primary/secondary Hypotension HTN Hypoaldosteronism High renin & Low renin& aldosterone aldosterone
Pseudohypoaldosteronism Gordon’s K sparing diuretics Cyclosporine Distal RTA
Loop diuretic testLoop diuretic test
Loop diuretic induces peak diuresis: 10ml/min
UK excretion>140μmeq/min
99αfludrocortisoneαfludrocortisone
Oral dose: 100μg2Hrs later If TTKG>10: hypoaldosteronism If TTKG<10: aldosterone minus
ENaC Chloride shunt
Aldosterone minusAldosterone minuslumen positive lumen positive
Slow Na reabsorption Fast Cl reabsorption
↓ECV ↑Renin Renal salt wasting
↑ECV or normal ↓Renin No renal salt wasting
Low aldosterone bioactivity Spirinolatone / ACEI / ARB Heparin / βblocker ↓ENaC Amiloride / Trimethoprim
Chloride ShuntGordon’s syndromeDrugs: CsADistal RTA
PseudoHypoAldosteronism: PseudoHypoAldosteronism: PHAPHA
Bonny et al, JASN 13: 2399-2414, 2002Bonny et al, JASN 13: 2399-2414, 2002
Clinical Gene Defects Type I: AR AD
Renal: salt wasting/hypo-Na Hyper-K Metabolic acidosis PAC↑/PRA↑Extra-renal: chest, GI, skin Renal : spontaneous remission
ENaCMineracorticoid receptor
Type II: AD ( Gordon syndrome )
Renal: HTN Hyper-K HCMA normal PAC; PRA↓
A: 1q31-q42 B: WNK4C: WNK1
Type III: Acquired (obstructive nephropathy; UTI; lead; amyloidosis)
GFR↓; Excessive salt lossHyper-KHCMAPAC↑/PRA↑Transient PHA
Main danger of hyperkalemiaMain danger of hyperkalemiaCardiac arrhythmiaCardiac arrhythmia
Onset Duration Calcium gluconate: 10%, 10 ~ 20cc as a bolus
Immediate < 5 min
30~ 60min
NaHCO3: 45 ~ 90meq
5~ 10 min 1~ 2 hours
Albuterol: 10 ~ 20mg inh, 10min
15 ~ 30 min 2~ 3 hours
Glucose/Insulin 15 ~ 30 min 3 ~ 4 hoursHD Immediate Several hoursK exchange resin 1~ 4 hours Few hours
Therapeutic principlesTherapeutic principlesWho to treat ?
Hospital admission is often recommended for patients with SK > 6 meq/L ; Interventions for any patient with SK >6.5 meq/L
To minimize membrane excitabilityTo shift potassium into cells
Skeletal muscle is the reservoir for more than 70% of body potassium
Promote potassium loss
Calcium gluconate IVCalcium gluconate IV Indications:
Cardiac irritability or SK > 7.5 meq/L 10ml of 10% calcium gluconate IV
as a bolus over 5 to 10 min Repeat it if no change in ECG is seen
after 5 to 10 min How it helps……? It protects the myocardium from toxicity to potassium but, there is concern about digoxin toxicity: an inhibitor of
Na-K ATPase, which increases intracellular calcium
Sodium bicarbonateSodium bicarbonate Uptake of K by skeletal muscle by favoring Na-
HCO3 cotransport and Na-H exchange, which, by increasing intracellular sodium, increases the activity of Na-K ATPase
HCO3 ceased to be a recommended intervention for acute hyperkalemia: studies showing that bicarbonate has little effect on the serum potassium concentration in stable hemodialysis patients, except for metabolic acidosis
HCO3 is a rational therapy to enhance potassium excretion in patients with intact kidney function
Insulin & glucose IVInsulin & glucose IV10 units of regular insulin in 50 ml of 50 %
dextrose (bolus) Initial bolus should be followed by
continuous infusion of 5% dextrose↓SK by about 1 meq/L within an hour
Infusion of RI at 20 U/H after a 6.6-U priming dose in a 70-kg healthy subject will rapidly raise insulin levels to approximately 500 μU/ml ( > 100 μU/ml ) with a near maximal kalemic effect But, to maintain euglycemia at these insulin levels, infusion of glucose at 40 g/H is required
Idealized plasma insulin levels after commonly used regimens in a patient with ESRD
beta-2 agonist albuterol beta-2 agonist albuterol (also called salbutamol)(also called salbutamol)
Inhalation/Nebulization/IV has been studied in stable hyperkalemic patients with end-stage renal disease.
SK falls by 0.3 ~ 0.6 meq /L within 30 minutes The doses via inhalation (the only formulation available
in the United States): 4 ~ 8 times those for the treatment of acute asthma
At high doses, albuterol may stimulate both beta-1 receptors, which can precipitate arrhythmias, and alpha-receptors, which cause K release from the liver and can transiently increase SK by >0.4 meq/L
Dialysate KDialysate K
predialysis plasma K dialysate K
>7.0 meq/L <2.0 meq/L
>5.5 2.0
Arrhythmia 2.5-3.0
On digitalis 2.5-3.0
Response of plasma potassium to potassium removal by dialysis
Change in PK at the end of a 3-hour dialysis against a zero potassium dialysate (blue ) and 2 hours after dialysis (red )
100 mmol of potassium removed ( 70-kg subject) at the end of dialysis (blue ) and 2 hours after dialysis (red )
Sodium polystyrene sulfonate Sodium polystyrene sulfonate (Kayexalate) (Kayexalate)Cation exchange resins: polymer
each gram eliminates 1 meq K Sodium polystyren sulphonate Promote exchange of Na for K in GI tract
25 to 50g with 100ml of 20% sorbitol
3 to 4 times a daySerious gastrointestinal complications:
fatal colonic perforation
PatiromerPatiromer Patiromer's (non-absorbable synthetic polymer ) active
groups are comprised of alpha-fluorocarboxylic acids that are paired with calcium ions rather than sodium: each gram eliminates 1 meq K
The acid groups are dissociated, allowing them to bind potassium↓, ammonium, and magnesium↓
It does not swell appreciably when exposed to water and it does not require a laxative to reach the distal colon
Patiromer was approved by the United States Food and Drug Administration in October 2015 and should be available in early 2016
Sodium zirconium Sodium zirconium cyclosilicate cyclosilicate (ZS-9)(ZS-9)
A crystal that is highly selective for K and ammonium ions through mechanisms that are very similar to those of naturally occurring ion channels
Na, Ca, and Mg are too small to form such stable bonds, making it thermodynamically unfavorable for them to be bound by the crystal
Because ZS-9 does not contain acid groups that dissociate, it binds potassium throughout the gastrointestinal tract Effective in the management of acute hyperkalemia
AddisonAddison’’s disease: s disease: partialpartialGagnon et al, NDT 2001Gagnon et al, NDT 2001
Hyponatremia Hyperkalemia or Normokalemia Mild hyperchloremic acidosis ↓Plasma anion gap: circulating cationic
sunstance ↑BUN and ↑Cr: modest ↑Hct UK excretion > 200meq/D Uald excretion↑ CCD flow rate↑
Aldosterone-ENaC Depolarizes Aldosterone-ENaC Depolarizes ROMK in CCD ROMK in CCD
E Na C
ROMK
Na K ATP aseDepolarize
+
Aldosterone+
Na
KV2R
AquaporinH2O CaSR
CaSR
K conservationK conservation
H+/K+- ATPase via MCD L/I: 0mM/>60mM→active process PPI use: ↓H+/K+- ATPase: UK +NaHCO3 wasting
↓Delivery via CCD
Progesterone in renal collecting duct Progesterone in renal collecting duct not just a sex hormone anymorenot just a sex hormone anymore
Progesterone+
KH
PR bound progesterone
HKα2 mRNA