Acute HyperkalemiaM Nagahama

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Acute Hyperkalemia

Division of NephrologySt. Luke’s international hospitalMasahiko Nagahama. MD. FASN

APSN Continuing Medical Education (CME) Course 2019June 20, 2019Nagoya Congress Center. JAPAN

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Acute Hyperkalemia

ACUTE HYPERKALEMIA

Breakout Group 5

Group 5: Acute HyperkalemiaEpidemiology and etiology

1. What is the prevalence of acute hyperkalemia in AKI?

2. What is the prevalence of hyperkalemia overall (e.g., in emergency department patients)?

3. What are the risk factors for development of acute hyperkalemia in AKI?

4. What are the risk factors/associated factors for development of acute hyperkalemia overall?

a. Medications associated with/leading to hyperkalemia?

b. Co-morbidities associated with/leading to hyperkalemia?

c. Sociodemographic factors (e.g., age distribution, ethnicity, sex)

5. What are the causes of hyperkalemia in AKI (in both common and rare conditions)?

6. What is the prevalence of concurrent electrolyte disorders (e.g., dysnatremias)?

Diagnosis

7. What are the optimal methods for measurement of acute hyperkalemia, and their accuracy (e.g., studies on accuracy of point-of-care testing versus laboratory [serology] measurement)

8. Value of additional diagnostic tests such as venous blood gas analysis, ECG?

9. What is the evidence on symptoms of hyperkalemia: are further studies indicated?

10. Are thresholds to define mild/moderate/severe hyperkalemia useful? Does

symptomatology depends on tolerance of patients? If so, what potassium thresholds should be used to define:

a. Severe hyperkalemia

b. Mild/moderate hyperkalemia

Management

11. What arrhythmias are associated with hyperkalemia, and at what potassium threshold?

12. What are the indications for use of intravenous calcium/sodium-bicarbonate, insulin and glucose, loop diuretics in hyperkalemia?

13. What ECG changes warrant calcium administration?

a. What is the evidence of the effectiveness of intravenous calcium to prevent

arrhythmia in hyperkalemia?

14. What is the comparative effectiveness of the various agents for acute management of hyperkalemia to shift potassium:

a. Timing of onset / b. Duration of effect

15. What is the comparative effectiveness of the various agents for acute management of hyperkalemia to bind/excrete potassium:

a. Timing of onset / b. Duration of effect

16. What is the optimal algorithm for the management of severe hyperkalemia

a. Setting for management / b. Treatment / c. Ongoing monitoring (i.e., frequency and

duration) / d. Evaluation of current medication and potential changes in medication

17. What is the optimal algorithm for the management of mild/moderate hyperkalemia

a. Setting for management / b. Treatment / c. Ongoing monitoring (i.e., frequency and duration)

Consequences18. What are the adverse consequences of acute hyperkalemia, and at what potassium thresholds:

a. Cardiovascular effects / b. Non-cardiovascular effects

19. Messages for patients (and follow-up doctors) with acute hyperkalemia:

a. Information concerning caution with concomitant medication use (e.g.,aldosterone-

antagonists, NSAIDs, etc…)5

“Acute Hyperkalemia”

• As distinct from chronic hyperkalemia, acute hyperkalemia is defined as a potassium result above the upper limit of normal, not known to be chronic.

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Prevalence of hyperkalemia• U.S : 3.6% - K > 5.0 mmol/L

Singer AJ et al. A retrospective study of emergency department potassium disturbances

Clin Exp Emerg Med. 2017

• Switzerland : 8.8% - K > 4.5 mmol/L, the upper limit of normal Pfortmuller CA et al.

Hyperkalemia in the emergency department Eur J Intern Med. 2013

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Acute HyperkalemiaM Nagahama

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Q7:

WHAT ARE THE OPTIMAL METHODS FOR

MEASUREMENT OF ACUTE HYPERKALEMIA, AND

THEIR ACCURACY (E.G., STUDIES ON ACCURACY

OF POINT-OF-CARE TESTING VERSUS

LABORATORY [SEROLOGY] MEASUREMENT)?

Central Laboratory vs Point of Care (POC)

Zhang et al. Analysis of bias in measurements of potassium, sodium and hemoglobin by an emergency department-based blood gas analyzer relative to hospital laboratory autoanalyzer results. PLoS One. 2015

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Central Laboratory

Point of Care(POC)

Mean±SD Mean±SD PMean bias(95%CI)

Potassium (mmol/L)

4.2±0.55 3.77±0.44 <0.00010.43

(0.38–0.48)

Specimentype

SerumWhole blood Li-heparin specimen

Serum

• Coagulation

– K is released from thrombocytes during blood clotting

• “Pseudohyper K” : Hyper K due to thrombocytosis

Q11:

WHAT ARRHYTHMIAS ARE

ASSOCIATED WITH

HYPERKALEMIA, AND AT WHAT

POTASSIUM THRESHOLD?67.5

26.2

31.8

23.8

12.6

6.9

2.1

1

0.5

0 20 40 60 80

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2

3

4

5

6

7

8

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Frequency of ECG abnormalities

10Comprehensive Clinical Nephrology 5 th edition Montague BT et al Clin J Am Soc Nephrol 2008

0

+30

-90

Threshold Potential

Resting Potential↑K

Na influx K efflux

↓K

Resting Potential; RP

↓

Action potential duration

↑↑

Refractory period

↑

↓K ↑K

Resting Potential; RP

↓ ↑

Action potential duration

↑↑ ↓

Refractory period

↑ ↓

↓K

Action potential in cardiomyocyte and ECG

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Mem

bra

ne

po

ten

tial

(m

V) ECG findings in hyperkalemia and adverse event

Characteristic Relative risk for adverse

event (95% CI)

Peaked T waves 0.77 (0.35-1.70)

PR prolongation 4.11 (0.88-19.28)

QRS prolongation 4.74 (2.01-11.15)

Bradycardia (HR<50 bpm) 12.29(6.69-22.57)

Junctional rhythm 7.46 (4.32-12.87)

Ventricular escaper rhythm 7.67 (5.28-11.13)

Ventricular tachycardia NA

2nd Degree heart block 6.92 (4.88-9.82)

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Durfey N et al. Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events? West J Emerg Med. 2017

Adverse events :symptomatic bradycardia,VT/VF, CPR, and/or death

• Slow depolarization afftects• PR amplitude• PR length• QRS duration• bundle branch• fascicular blocks

• Fast repolarization affects• ST segment• T wave amplitude/shape

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Acute HyperkalemiaM Nagahama

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Calcium for hyperkalemic ECG changes

• Mechanism

– Ca directly antagonizes the membrane effects of hyper K : “membrane stabilization”

– Ca accelerates Ca dependent conduction in depolarization

• Indication : wide QRS complexes (depolarization problem)

Ca Chloride Ca Gluconate

Ca delivery 270mg (13.5 mEq) / g 90mg (4.5 mEq) / g

Dose 0.5g to 1.0 g 1.0g

Preferred Ca source ✓

Risk of extravasation ✓

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Emergency Cart at St. Luke’s

14Ngahama et al. “Resident manual 9th edition” 2019 Igaku shoin

Ca Gluconate 10ml (850mg)78.5mg of Ca

Hyperkalemic ECG changes

• ECG changes in hyperkalemia are associated with a variety of change.– peaked T wave / prolonged PR / wide QRS / P wave disappearance

• The sequence is reported to be peaked T waves, prolonged PR interval, progressive widening of QRS complex, followed by “sine wave” patterns, ventricular fibrillation and asystole.

• ECG manifestations may be difficult to determine, particularly with superimposed underlying structural heart disease and/or ischemia. Furthermore, there is great variability between studies in who interpreted the ECG, how proximal in time potassium levels and ECG were measured, and whether ECGs were compared to prior ECGs.

• We recommend continuous cardiac monitoring as well as performing a 12-lead ECG.

Montague BT et al Clin J Am Soc Nephrol 2008Aslam S et al, Nephrol Dial Transplant 2002

Acker CG et al, Arch Intern Med 1998Szerlip HM et al, Weiss J, Am J Kidney Dis 1986

KDIGO Controversies Conference on Potassium Management“Acute Hyperkalemia” Group 5 draft

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Q17:

WHAT IS THE OPTIMAL ALGORITHM FOR THE MANAGEMENT OF

HYPERKALEMIA WITH RESPECT TO:a. SETTING FOR MANAGEMENT

b. TREATMENT

c. ONGOING MONITORING (I.E., FREQUENCY AND DURATION)d. EVALUATION OF CURRENT MEDICATIONS AND POTENTIAL

CHANGES IN MEDICATIONS

e. INDICATION FOR DIALYSIS

K>6.0 mmol/L

Place on monitor

12 lead ECG

Repeat POC if possible

ECG

changesIV calcium salts**

Consider K binder

and IV furosemide

Consider

dialysis****

YesNo

<6.0

mmol/L

Repeat K>6.0 mmol/L

YesNo

High risk for

HK

Yes*

>6.0 mmol/L<6.0 mmol/L

Exit

Exit

Repeat KNo

If no POC

Yes

AKI or CKD

No

Exit

Consider GFR,

volume, &

airway status

IV insulin/glucose

and/or

2 agonist***

and/or

IV bicarbonate if

acidosis

Assess/manage

underlying

etiology

Reassess K

frequently

KDIGO Controversies Conference on

Potassium Management

“Acute Hyperkalemia” Group 5 draft Limited evidence of NaHCO3 for hyper K

Elliott et al. Management of patients with acute hyperkalemia CMAJ 2010

Emergency interventions for hyperkalaemia The Cochrane Collaboration 2005 Pharmacological interventions for the acute management of hyperkalaemia in adults The Cochrane

Collaboration 2015

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Acute HyperkalemiaM Nagahama

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Change in plasma K with treatment for (anuric) dialysis patients

Pla

sma

K（

mEq

/L）

minutes

Blumberg A et al. Effect of prolonged bicarbonate administration on plasma potassium in terminal renal failure

Kidney Int 1992

Blumberg A et al. Effect of various therapeutic approaches on plasma potassium and major regulating factors in

terminal renal failure Am J of Med 1988

Plasma K(mEq/L)5.44 /4hrs (P < 0.05)5.30/6hrs (P < 0.01)

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Regulation of renal K secretion- K secretion in collecting duct -

• Distal tubular Na delivery①

• Distal tubular flow②

• Lumen electronegativity③

• Aldosterone④

• Serum K concentration⑤

Na+Na+

Na+

K+K+

K+

Aldosterone

ー

ー

ーー

①, ②

④

③

Cortical Collecting Duct

Regulation of renal K secretion- NaHCO3 and Furosemide -

• Distal tubular Na delivery①

• Distal tubular flow②

• Lumen electronegativity③

• Aldosterone④

• Serum K concentration⑤

Na+Na+

Na+

K+K+

K+

Aldosterone

ー

ー

ーー

①, ②

④

③

Cortical Collecting Duct

Lumen electronegativity : HCO3- > Cl-

K secretion : NaHCO3 > NaCl

NaHCO3 solutions

SolutionNa+

(mEq/L)Cl-

(mEq/L)HCO3

-

(mEq/L)

Hypertonic NaHCO3

(7%)833 833

Hypertonic NaHCO3

(8.4%)1000 1000

Isotonic NaHCO3

(1.26%)150 150

Normal saline 154 154

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CaseHPI• A 55 y.o male is brought to the ED by family due to worsening

muscle weakness. He has been feeling feverish for a week and took NSAIDs for several times. Has had weakness in his legs and difficulty in walking since yesterday. Then, he started feeling weak in his arms, too.

• Does not complain of any pain or numbness.• Denies any history of trauma.

PMH• HTN, DM and CKD stage 3

(eGFR: 34ml/min/1.73m2) • Admitted for CAD s/p PTCA 3 yrs ago • Admitted for CHF 1yr ago

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Medications• Aspirin 81mg daily• Lisinopril 10mg daily• Spironolactone 50mg daily• Carvedilol 2.5mg daily• Amlodipine 10mg daily• Lipitor 10mg daily• Insulin glargine 20U, R 5-5-5

CasePhysical examination• VS: Temp 37.2℃, BP 118/60, HR 98, RR 22 (POx: 98% on RA)• General: Alert, oriented, pleasant, white female in no apparent

distress, lying comfortably in bed.• HEENT: neck was supple• Lungs: trachea was central, air entry equal, no rhonchi or creps• Heart: nl S1&S2, 2/6 systolic M @ Lt sternal boarder• Abd: a median laparotomy scar that was well-healed and showed no

dehiscence or hernias. nl BS• Extremity: pulses were equal in all limbs, (+) mild pitting edema• Neuro

– CNS: CN intact– Motor: Upper: proximal 5/5 and distal 5/5, Lower: proximal 5/5

and distal 5/5– DTR: intact throughout– Sensory: intact– Cerebellar sign: negative

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Acute HyperkalemiaM Nagahama

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Case

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Laboratory data

Blood

Na+ 130 mEq/L

K+ 6.8 mEq/L

Cl- 111 mEq/L

BUN 94 mg/dL

Cr 2.7 mg/dL

Blood

Na+ 135 mEq/L

K+ 4.8 mEq/L

Cl- 108 mEq/L

BUN 44 mg/dL

Cr 1.7 mg/dL

On admission 1M ago @ clinic

In summary

• 55 yo M with HTN, DM, CAD s/p PTCA and CKD stage 3 on ACE-I and spironolactone came in a few days h/o fever and worsening weakness, who was found to have K 6.8.

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Treatment of Hyperkalemia

Therapy Mechanism Onset Duration

Calcium saltsAntagonize membrane effects

1-3 min 30-60 min

InsulinPotassium redistribution

30 min 4-6 hr

β2-Adrenergic agonist 30 min 2-4 hr

NaHCO3

Potassium removal

30-60min

K-binders (SPS etc.) 1-2 hr 4-6 hr

Hemodialysis ImmediateUntil HD completed

Disorders of Potassium Metabolism. Comprehensive Clinical Nephrology 5 th edition

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Questions to be answered to manageacute hyperkalemia

• True hyperkalemia?

• Vital sign (make sure arrhythmia not happening)

• Glucose?

• HCO3-?

• Urine output?

• ECG ?

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Questions to be answered to manageacute hyperkalemia

• True hyperkalemia?⇒ R/Oed Hemolysis

• Vital sign (make sure arrhythmia not happening)⇒Temp 37.2℃, BP 118/60, HR 98, RR 22

• Glucose?⇒ Glu 140 mg/dL

• HCO3-?

⇒ HCO3- 14

• Urine output?⇒ some, but not measured

• ECG ?⇒ Peaked T wave

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Management for acute hyperkalemiafor this case (opinion)

1. Place continuous cardiac monitor / ECG.

2. Give Ca gluconate 10ml (1 ampule) IV over 2-5 minutes.

3. Give 10U Insulin＋50% Dextrose 50ml.

4. Give Furosemide 100mg IV and NaHCO3 at 200ml/hr.

5. Place Foley and monitor urine out put closely.

6. If urine output < 100ml/hr, will consider emergent HD (HD Ns called in).

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Acute HyperkalemiaM Nagahama

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Take home messages• Serum K is slightly higher than that in plasma or whole blood due to K

release from coagulation, which is clinically ignorable in normal situations.

• ECG changes in hyperkalemia is divided to depolarization abnormalities (prolonged PR / wide QRS / P wave disappearance) and repolarization abnormalities (peaked T wave).

• Ca is indicated for depolarization abnormalities in hyper K.

• Continuous cardiac monitoring is more important than ECG alone in hyper K.

• IV Isotonic NaHCO3 (1.26%) and Furosemide use could be considered for hyper K, if acidosis and good urine output exist (opinion!!).

Thank you

managaha@luke.ac.jp32

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