Lecture I gave the nephrology fellows

1. Hyperkalemia
recent case and some notes for boards

2. • Patient transfered from nursing home
• Altered mental status
• Decreased PO
• Diarrhea

3. 5:24 pm
Initial labs
Na 128 Cl 103 BUN 100
HCO3 9 Cr 5.6
Repeat ordered to include
potassium
Cr on last admission was 1.7

4. Problem list

5. Problem list
• Acute renal failure
• Metabolic acidosis
• Hyponatremia

6. What do you next
The repeat blood draw with the potassium doesn’t
come back for 64 minutes

7. EKG done at 18:06

8. What’s your differential if the K
was 7 but the EKG looked like this?

9. Differential
• True hyperkalemia • Lower ambient
temperatures are a risk
• Pseudohyperkalemia
• More likely in winter
• traumatic blood draw
• A low serum Calcium
• small bore needles
can indicate
• hand pumping pseudohyperkalemia
• exercise
• hematologic diseases
• All of these are made • thrombocytosis
worse by ß-blockers
• >400,000
• leukocytosis
• >100,000

10. EKG Changes with
hyperkalemia
• Peaking of T waves
• look for V2, 3, and 4
• ST-segment depression
• Widening of the PR interval
• Widening of the QRS interval
• Loss of the P wave
• Development of a sine-wave pattern
• The appearance of a sine-wave
pattern is ominous and is a harbinger
of impending V-fib and asystole

11. EKG Changes with
hyperkalemia
• Peaking of T waves
• look for V2, 3, and 4
• ST-segment depression
• Widening of the PR interval
• Widening of the QRS interval
• Loss of the P wave
• Development of a sine-wave pattern
• The appearance of a sine-wave
pattern is ominous and is a harbinger
of impending V-fib and asystole

12. EKG Changes with
hyperkalemia
• Peaking of T waves
• look for V2, 3, and 4
• ST-segment depression
• Widening of the PR interval
• Widening of the QRS interval
• Loss of the P wave
• Development of a sine-wave pattern
• The appearance of a sine-wave
pattern is ominous and is a harbinger
of impending V-fib and asystole

13. Zip code

14. • An old study on the sensitivity and specificity of EKG for
hyperkalemia
• Sensitivity of 35-43%
• Specificity of 85%
• using the EKGs alone resulted in missing over half
the cases of hyperkalemia
• 15% of patients identified as having hyperkalemia by
EKG had a normal potassium
Wrenn et al. The ability of physicians to predict hyperkalemia from the
ECG. Annals of emergency medicine (1991) vol. 20 (11) pp. 1229-32

15. • Community hospital
• Inclusion criteria
• K>6
• EKG done within an hour of the blood draw.
• Exclusion criteria
• hemolyzed specimens
• cardiac pacing or other conditions which
masked EKG changes
• Lack of a paper chart
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

16. • All EKGs were graded • Each EKG was classified
with respect to: by the following criteria
• Rate
• Intervals
• ST deflection
• T wave inversion
• magnitude and
duration of the P, R
and T waves
• The reading
cardiologist’s official
diagnosis
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

17. 250 patients with diagnosis of hyperkalemia
19 without hyperkalemia
68 with K<6.0
50 without an EKG
23 not identified
90 patients included in the analysis
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

18. • Age 20-93
• Median age 73
• ß-blockers: 49
• ACEi: 31
• Loop diuretics: 30
• Obstruction: 11
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

19. • Age 20-93
• Kayexylate: 75
• Median age 73
• Calcium: 60
• ß-blockers: 49
• Insulin: 62
• ACEi: 31
• Follow up K measured 5 hours
after initial draw
• Loop diuretics: 30
• Average K was 5.8
• Obstruction: 11
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

20. Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

21. • Reading cardiologist: • Investigators:
• T-wave “findings”: 24 • QRS widening: 6
• peaked T: 3 • peaked T: 29
• Strict criteria: 16
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

22. • Reading cardiologist: • Investigators:
• T-wave “findings”: 24 • QRS widening: 6
• peaked T: 3 • peaked T: 29
• Strict criteria: 16
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30

23. • Sensitivity of strict criteria: 18%
• Sensitivity of any EKG change 52%
• Acidosis decreased the likelihood of peaked T-
waves
• T-waves were easiest to review in the lead with
the greatest R-wave deflection
• V2, V3, or V4 in 85% of patients

24. ECG changes were
Strict
in only one of 14
noted
hyperkalemic patients who
arrhythmias or
manifested
cardiac arrest. Only
seven had any T-wave
changes

25. ...which calls into question the
prognostic use of the ECG in this
Given the poor
setting.
sensitivity and specificity
of the ECG, the authors
stressed that the clinical scenario and
serial measurements of K+
are the preferred tools to guide the
treatment of patients...

26. Hyperkalemic Brugada Sign

27. • Brugada syndrome
• Autosomal dominant cause of sudden
cardiac death
• EKG is characterized by ST elevation, coved
QT interval and right bundle branch pattern
of QRS prolongation
• EKG deteriorate from NSR to Brugada sign
to polymorphic ventricular tachycardia

28. • Brugada sign has been reported to occur with
hyperkalemia
Littmann et al. The hyperkalemic Brugada sign. Journal of
electrocardiology (2007) vol. 40 (1) pp. 53-9

29. Littmann et al. The hyperkalemic Brugada sign. Journal of
electrocardiology (2007) vol. 40 (1) pp. 53-9

30. Littmann et al. The hyperkalemic Brugada sign. Journal of
electrocardiology (2007) vol. 40 (1) pp. 53-9

31. Potassium
6:28 pm
finally
Na 128 Cl 103 BUN 100
HCO3 9 Cr 5.6
Potassium = 9.9

32. Has the danger of hyperkalemia
been exaggerated?

33. E
P
O
Has the danger of hyperkalemia
N
been exaggerated?

34. • Prospective study of 476 patients in 5 Italian
hemodialysis units.
• 3 years
• 167 deaths
• 35 due to CVD (not SCD)
• 32 due to sudden cardiac death (unexpected,
non-traumatic, death within 1 hour of
symptom onset)
Genovesi et al. Sudden death and associated factors in a historical cohort
of chronic haemodialysis patients. Nephrol Dial Transplant (2009) pp.

37. • Risk factors for sudden cardiac death in non-
dialysis patients include:
• heart failure
• LVH
• Valvular disease
• None of these were significant in dialysis
patients
Genovesi et al. Sudden death and associated factors in a historical cohort
of chronic haemodialysis patients. Nephrol Dial Transplant (2009) pp.

38. MWF: Mon* Tues Wed Thurs Fri Sat Sun
TTS: Tues* Wed Thurs Fri Sat Sun Mon
* in the 24 hours after dialysis

39. MWF: Mon* Tues Wed Thurs Fri Sat Sun
TTS: Tues* Wed Thurs Fri Sat Sun Mon
* in the 24 hours after dialysis

40. p=0.02
MWF: Mon* Tues Wed Thurs Fri Sat Sun
TTS: Tues* Wed Thurs Fri Sat Sun Mon
* in the 24 hours after dialysis

41. Potassium
6:28 pm
finally
Na 128 Cl 103 BUN 100
HCO3 9 Cr 5.6
Potassium = 9.9

42. What do you next?

43. Immediate treatment:
Calcium
• What kind
• How much
• How often

44. Immediate treatment:
Calcium
• What kind
• calcium chloride if central access
• otherwise calcium gluconate

45. Calcium
• Calcium Chloride
• Strength: 10ml (10%) contains 13.5mEq
(272mg) Ca
• Ca Gluconate
• Strength: 10ml (10%) contains 4.65mEq
(93mg) Ca

46. Immediate treatment:
Calcium
• How often: repeat every 5 minutes until the
EKG corrects

47. Contraindications to Ca

48. Contraindications to Ca
• Digoxin toxicity

49. Contraindications to Ca
RE
AL
LY?
• Digoxin toxicity

50. • In animal models, calcium potentiates digoxin
toxicity (20 mg/dL and 23 mg/dL)
• Dose-dependent toxicity
related to rate of calcium
infusion
• Irreversible contraction
Stone heart theory
• Calcium binding to
troponin-C
Lown B, Black H, Moore FD. Digitalis, electrolytes, and the
surgical patient. Am J Cardiol 1960;6:309 –37.

52. • All patients with diagnosis of digoxin toxicity
at a single tertiary care hospital from 1989 to
2005.
• 2059 patients with elevated dig was weaned to
161 with signs and symptoms consistent with
toxicity
• 32/159 patients
died (20%)
• 5/23 calcium
patients died
(P=0.78)

53. • With multivariate analysis only hyperkalemia
was associated with increased mortality.

54. In the original paper by Bower and Mengle, 2 patients
were presented. The first case occurred in 1933, and
involved a 55-year-old man with bilateral femur fractures
who was felt to have either multiple myeloma or
hyperparathyroidism. He underwent a right-sided
thyroidectomy and “possible” parathyroidectomy. This
patient had received 8.5 cc of Digalen (a purified digitalis
preparation available from 1904 –1964) over 20 h. On the
second post-operative day, he was noted to have a fine
tremor in both hands, which was felt to possibly be
“beginning tetany.” The patient was given 10 cc of 10%
calcium chloride intravenously, and shortly thereafter
died.
Bower JO, Mengle HAK. The additive effect of calcium and digitalis: a
warning, with a report of two deaths. JAMA 1936;106: 1511–53.

55. The second case occurred in 1935, and involved a previously
healthy 32-year-old woman who presented with nausea, vomiting,
and abdominal pain. She underwent a cholecystectomy, during
which a single gallstone and hemorrhagic bile were found. On
post-operative day 2, she received several doses of Digalen for a
heart rate of 100 beats/min and a blood pressure of 90/50 mm Hg.
By the sixth post-operative day, she had received approximately 15
cc of Digalen, and the heart rate was 120 beats/min. More than 24
h after the last dose of Digalen, she received 10 cc of 10% calcium
gluconate through a peripheral intravenous line for rate control.
Approximately 2 min later, the pupils were dilated, and “she had a
generalized convulsion with only slight muscular fibrillations.” She
was pronounced dead shortly thereafter.
Neither of these patients had any documentation of the type of
dysrhythmia, and there was no mention of any cardiac-glycoside
toxic symptoms (i.e., nausea, vomiting, anorexia, fatigue, visual
disturbances, etc.) before the administration of calcium gluconate.
Serum levels of Digalen were not available.
Bower JO, Mengle HAK. The additive effect of calcium and digitalis: a
warning, with a report of two deaths. JAMA 1936;106: 1511–53.

56. Bilbault et al. European journal of emergency medicine : official journal
of the European Society for Emergency Medicine (2009) pp.

57. Bilbault et al. European journal of emergency medicine : official journal
of the European Society for Emergency Medicine (2009) pp.

58. Induce intracellular shift
• Insulin and glucose
• primary side effect is hypoglycemia
• Albuterol
• primary side effect is tachycardia
• 20 mg by nebulizer

59. Induce intracellular shift
0.3
0.1
-0.1 0 10 20 30 40 50 60
Change in K
-0.3
-0.5
-0.7
-0.9
-1.1
-1.3
-1.5
Time (min)
NaHCO3 8.4% NaHCO3 1.4%
Epinephrine Insulin Glucose
Dialysis
Blumberg Et al. Amer J Med; 1988: 85, 507-512.

60. 0.4 0.0
0 15 30 45 60
0.2
-0.3
0.0
0 30 60 90 120
Change in K
Change in K
-0.6
-0.2
-0.4 -0.9
-0.6
-1.2
-0.8
-1.0 -1.5
Time (min) Time (min)
Saline 10 mg 20 mg Insulin Albuterol Combination
Allon Et al. Annals of Int Med; 1989: 110, 426-429. Allon Et al. Kidney International; 1990: 38, 869-872.

61. Sodium bicarbonate
• Doesn’t lower the potassium
• Does lower ionized calcium

62. 0.2
0.1
Change in K
0.0
0 10 20 30 40 50 60
-0.1
-0.2
Time (min)
NaHCO3 8.4% NaHCO3 1.4%
Blumberg Et al. Kidney International; 1992: 41, 369-374. Blumberg Et al. Amer J Med; 1988: 85, 507-512.
0.2 0.4
0.2
0.0
0 15 30 45 60
0.0
-0.2
Change in K
Change in K
0 15 30 45 60
-0.2
-0.4
-0.4
-0.6
-0.6
-0.8 -0.8
-1.0 -1.0
Time (min) Time (min)
HCO3 Saline HCO3 + Insulin Saline + Insulin
Allon Et al. Amer J Kidney Dis; 1996: 28, 508-514.

63. bicarbonate may cause harm
• Increasing pH will decrease the ionized
calcium, predisposing to hyperkalemia induced
arrhythmia

64. Remove potassium
• Loop diuretics and saline
• Sodium polystyrene sulfonate
• Dialysis

65. Dialysis
Two hours on a 11:00 pm
one K bath

66. Etiologies of hyperkalemia
• Exogenous intake • Transcellular shift
• Rare • Digoxin
• Requires large doses • Beta-blockers
• Endogenous sources • DKA
• Tumor lysis syndrome • Metabolic acidosis
• Rhabdomyolysis • Decreased renal excretion
• Hemolysis • Renal failure
• Medications

67. ACEi, Aldo Ant and potassium
• ACEi combined with aldosterone antagonists
reduce mortality with heart failure
• Combination therapy may have a role in
decreasing the progression of CKD
• Placebo controlled RCT to look at renal
potassium handling in CKD (eGFR 25-65 mL/
min) with dual blockade
• 18 CKD patients crossed over to both placebo
and active treatments
• Additional 18 gender matched control group with
eGFR >100
Preston et al. Hypertension (2009)

68. • 18 CKD patients crossed over to both placebo
(control group 1) and combination therapy
• Additional 18 gender matched control group with
eGFR >100 (control group 2)
• Primary end point: potassium excretion (mmol/
h) at 2 and 3 hours after 35 mmol of oral KCl
• measured after 3 days on controlled diet (20
mmol of Na and 50 mmol of K)
• Secondary end point ambulatory potassium
after 4 weeks of therapy
Preston et al. Hypertension (2009)

70. CKD
washout
2 weeks
Randomize

71. Placebo
No CKD
40 mg Lisinopril and
25 mg Spironolactone
Treatment period 1
CKD
4 weeks
washout
2 weeks
Placebo
Randomize
35 mmol KCl challenge

72. Placebo
No CKD
40 mg Lisinopril and
25 mg Spironolactone Cross-over
Treatment period 1 washout
CKD
4 weeks 2 weeks
washout
2 weeks
Placebo
Randomize
35 mmol KCl challenge

73. Placebo
No CKD
40 mg Lisinopril and
25 mg Spironolactone Cross-over Placebo
Treatment period 1 washout Treatment period 2
CKD
4 weeks 2 weeks 4 weeks
washout
2 weeks
Placebo 40 mg Lisinopril and
25 mg Spironolactone
Randomize
35 mmol KCl challenge 35 mmol KCl challenge

75. Placebo
GFR >100 CKD (GFR 25-65)
46%
96%
4% 54%
The control was able to excrete 96% of the potassium load within 5
hours, while the CKD group cleared less than half of the potassium.

76. • Serum potassium was identical
for placebo CKD patients and
control patients at baseline
(P=0.25) and hour 3 (P=0.8)
• Decreased renal excretion
but no change in serum
potassium indicates increas-
ed extra-renal potassium
handling
GFR > 100 CKD
30.0
P=0.02 P=0.09
22.5
15.0
7.5
0
Aldo Insulin

77. • In the CKD patients,
Placebo versus dual Rx:
significant increase in
potassium
Placebo Dual Rx
150 P=0.006 P=0.013
135
120
• Significant reduction in 123
blood pressure 90
80 75
60
30
Systolic Diastolic

78. • Difference in hourly potassium excretion went from
3.75 to 3.31 mmol/h (nl GFR was >10)
• Higher peak K (4.72 vs. 5.35)
• No difference in total potassium excreted in 5 hours
(P=0.14)

79. • Change in potassium following the 35 mmol
challenge predicted the change in potassium
following 1 week on combination therapy

80. The authors conclude that the
i n c re a s e d i n b a s e l i n e
potassium a n d d y n a m i c
potassium is due to lisinopril and
spironolactone induced changes in
extra-renal potassium handling