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Hyperkalemia
recent case and some notes for boards
• Patient transfered from nursing home

• Altered mental status

• Decreased PO

• Diarrhea
5:24 pm
     Initial labs
Na 128   Cl 103 BUN 100
         HCO3 9   Cr 5.6

Repeat ordered to include
potassium

Cr on las...
Problem list
Problem list


• Acute renal failure
• Metabolic acidosis
• Hyponatremia
What do you next
The repeat blood draw with the potassium doesn’t
           come back for 64 minutes
EKG done at 18:06
What’s your differential if the K
was 7 but the EKG looked like this?
Differential
• True hyperkalemia          • Lower ambient
                               temperatures are a risk
• Pseudohy...
EKG Changes with
            hyperkalemia
• Peaking of T waves
   • look for V2, 3, and 4
• ST-segment depression
• Wideni...
EKG Changes with
            hyperkalemia
• Peaking of T waves
   • look for V2, 3, and 4
• ST-segment depression
• Wideni...
EKG Changes with
            hyperkalemia
• Peaking of T waves
   • look for V2, 3, and 4
• ST-segment depression
• Wideni...
Zip code
• An old study on the sensitivity and specificity of EKG for
  hyperkalemia




    • Sensitivity of 35-43%
    • Specificit...
• Community hospital
• Inclusion criteria
  • K>6
  • EKG done within an hour of the blood draw.
• Exclusion criteria
  • ...
• All EKGs were graded            • Each EKG was classified
 with respect to:                   by the following criteria

...
250 patients with diagnosis of hyperkalemia

     19 without hyperkalemia
     68 with K<6.0
     50 without an EKG

     ...
• Age 20-93

• Median age 73

• ß-blockers: 49

• ACEi: 31

• Loop diuretics: 30

• Obstruction: 11
                      ...
• Age 20-93
                        • Kayexylate: 75
• Median age 73
                        • Calcium: 60
• ß-blockers: 4...
Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30
• Reading cardiologist:           • Investigators:
 • T-wave “findings”: 24             • QRS widening: 6
 • peaked T: 3   ...
• Reading cardiologist:           • Investigators:
 • T-wave “findings”: 24             • QRS widening: 6
 • peaked T: 3   ...
• Sensitivity of strict criteria: 18%

• Sensitivity of any EKG change 52%

• Acidosis decreased the likelihood of peaked ...
ECG changes were
Strict
         in only one of 14
noted
hyperkalemic patients who
        arrhythmias or
manifested
cardi...
...which calls into question the
prognostic use of the ECG in this
           Given the poor
setting.
sensitivity and spec...
Hyperkalemic Brugada Sign
• Brugada syndrome

  • Autosomal dominant cause of sudden
   cardiac death

  • EKG is characterized by ST elevation, cov...
• Brugada sign has been reported to occur with
 hyperkalemia




                 Littmann et al. The hyperkalemic Brugada...
Littmann et al. The hyperkalemic Brugada sign. Journal of
               electrocardiology (2007) vol. 40 (1) pp. 53-9
Littmann et al. The hyperkalemic Brugada sign. Journal of
               electrocardiology (2007) vol. 40 (1) pp. 53-9
Potassium
                           6:28 pm
       finally
Na 128   Cl 103 BUN 100
         HCO3 9   Cr 5.6

Potassium = 9...
Has the danger of hyperkalemia
      been exaggerated?
E
                 P
        O
Has the danger of hyperkalemia


      N
      been exaggerated?
• Prospective study of 476 patients in 5 Italian
 hemodialysis units.

• 3 years

• 167 deaths

  • 35 due to CVD (not SCD...
• Risk factors for sudden cardiac death in non-
 dialysis patients include:

  • heart failure

  • LVH

  • Valvular dise...
MWF:   Mon*    Tues   Wed     Thurs   Fri            Sat             Sun
TTS:   Tues*   Wed    Thurs   Fri     Sat        ...
MWF:   Mon*    Tues   Wed     Thurs   Fri            Sat             Sun
TTS:   Tues*   Wed    Thurs   Fri     Sat        ...
p=0.02




MWF:   Mon*    Tues   Wed        Thurs   Fri            Sat             Sun
TTS:   Tues*   Wed    Thurs      Fr...
Potassium
                           6:28 pm
       finally
Na 128   Cl 103 BUN 100
         HCO3 9   Cr 5.6

Potassium = 9...
What do you next?
Immediate treatment:


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


              Calcium
• What kind
  • calcium chloride if central access
  • otherwise calcium gluc...
Calcium
• Calcium Chloride
  • Strength: 10ml (10%) contains 13.5mEq
    (272mg) Ca

• Ca Gluconate
  • Strength: 10ml (10...
Immediate treatment:



              Calcium
• How often: repeat every 5 minutes until the
 EKG corrects
Contraindications to Ca
Contraindications to Ca




• Digoxin toxicity
Contraindications to Ca


RE
            AL
                     LY?
• Digoxin toxicity
• In animal models, calcium potentiates digoxin
 toxicity (20 mg/dL and 23 mg/dL)

• Dose-dependent toxicity
 related to r...
• All patients with diagnosis of digoxin toxicity
 at a single tertiary care hospital from 1989 to
 2005.

• 2059 patients...
• With multivariate analysis only hyperkalemia
 was associated with increased mortality.
In the original paper by Bower and Mengle, 2 patients
were presented. The first case occurred in 1933, and
involved a 55-ye...
The second case occurred in 1935, and involved a previously
healthy 32-year-old woman who presented with nausea, vomiting,...
Bilbault et al. European journal of emergency medicine : official journal
           of the European Society for Emergency ...
Bilbault et al. European journal of emergency medicine : official journal
           of the European Society for Emergency ...
Induce intracellular shift

• Insulin and glucose
  • primary side effect is hypoglycemia
• Albuterol
  • primary side effec...
Induce intracellular shift

                   0.3
                   0.1
                  -0.1 0       10   20   30     ...
0.4                                                             0.0
                                                      ...
Sodium bicarbonate



• Doesn’t lower the potassium
• Does lower ionized calcium
0.2



                                                                                                             0.1


...
bicarbonate may cause harm



• Increasing pH will decrease the ionized
 calcium, predisposing to hyperkalemia induced
 ar...
Remove potassium


• Loop diuretics and saline
• Sodium polystyrene sulfonate
• Dialysis
Dialysis
Two hours on a   11:00 pm
 one K bath
Etiologies of hyperkalemia
• Exogenous intake         • Transcellular shift
  • Rare                      • Digoxin
  • Re...
ACEi, Aldo Ant and potassium
• ACEi combined with aldosterone antagonists
 reduce mortality with heart failure
• Combinati...
• 18 CKD patients crossed over to both placebo
 (control group 1) and combination therapy

• Additional 18 gender matched ...
CKD
      washout
      2 weeks



          Randomize
Placebo

                No CKD

                          40 mg Lisinopril and
                         25 mg Spironolact...
Placebo

                No CKD

                          40 mg Lisinopril and
                         25 mg Spironolact...
Placebo

                No CKD

                          40 mg Lisinopril and
                         25 mg Spironolact...
Placebo




         GFR >100                          CKD (GFR 25-65)

                                              46%
...
• Serum potassium was identical
   for placebo CKD patients and
   control patients at baseline
   (P=0.25) and hour 3 (P=...
• In the CKD patients,
  Placebo versus dual Rx:
  significant increase in
  potassium

                                  P...
• 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)...
• Change in potassium following the 35 mmol
 challenge predicted the change in potassium
 following 1 week on combination ...
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 lisin...
Whats New In Potassium
Whats New In Potassium
Whats New In Potassium
Whats New In Potassium
Whats New In Potassium
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Whats New In Potassium

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Lecture I gave the nephrology fellows

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Whats New In Potassium

  1. 1. Hyperkalemia recent case and some notes for boards
  2. 2. • Patient transfered from nursing home • Altered mental status • Decreased PO • Diarrhea
  3. 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. 4. Problem list
  5. 5. Problem list • Acute renal failure • Metabolic acidosis • Hyponatremia
  6. 6. What do you next The repeat blood draw with the potassium doesn’t come back for 64 minutes
  7. 7. EKG done at 18:06
  8. 8. What’s your differential if the K was 7 but the EKG looked like this?
  9. 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. 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. 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. 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. 13. Zip code
  14. 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. 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. 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. 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. 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. 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. 20. Montague et al. Clin J Am Soc Nephrol (2008) 3 pp. 324-30
  21. 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. 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. 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. 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. 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. 26. Hyperkalemic Brugada Sign
  27. 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. 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. 29. Littmann et al. The hyperkalemic Brugada sign. Journal of electrocardiology (2007) vol. 40 (1) pp. 53-9
  30. 30. Littmann et al. The hyperkalemic Brugada sign. Journal of electrocardiology (2007) vol. 40 (1) pp. 53-9
  31. 31. Potassium 6:28 pm finally Na 128 Cl 103 BUN 100 HCO3 9 Cr 5.6 Potassium = 9.9
  32. 32. Has the danger of hyperkalemia been exaggerated?
  33. 33. E P O Has the danger of hyperkalemia N been exaggerated?
  34. 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.
  35. 35. • 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.
  36. 36. MWF: Mon* Tues Wed Thurs Fri Sat Sun TTS: Tues* Wed Thurs Fri Sat Sun Mon * in the 24 hours after dialysis
  37. 37. MWF: Mon* Tues Wed Thurs Fri Sat Sun TTS: Tues* Wed Thurs Fri Sat Sun Mon * in the 24 hours after dialysis
  38. 38. 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
  39. 39. Potassium 6:28 pm finally Na 128 Cl 103 BUN 100 HCO3 9 Cr 5.6 Potassium = 9.9
  40. 40. What do you next?
  41. 41. Immediate treatment: Calcium • What kind • How much • How often
  42. 42. Immediate treatment: Calcium • What kind • calcium chloride if central access • otherwise calcium gluconate
  43. 43. Calcium • Calcium Chloride • Strength: 10ml (10%) contains 13.5mEq (272mg) Ca • Ca Gluconate • Strength: 10ml (10%) contains 4.65mEq (93mg) Ca
  44. 44. Immediate treatment: Calcium • How often: repeat every 5 minutes until the EKG corrects
  45. 45. Contraindications to Ca
  46. 46. Contraindications to Ca • Digoxin toxicity
  47. 47. Contraindications to Ca RE AL LY? • Digoxin toxicity
  48. 48. • 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.
  49. 49. • 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)
  50. 50. • With multivariate analysis only hyperkalemia was associated with increased mortality.
  51. 51. 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.
  52. 52. 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.
  53. 53. Bilbault et al. European journal of emergency medicine : official journal of the European Society for Emergency Medicine (2009) pp.
  54. 54. Bilbault et al. European journal of emergency medicine : official journal of the European Society for Emergency Medicine (2009) pp.
  55. 55. Induce intracellular shift • Insulin and glucose • primary side effect is hypoglycemia • Albuterol • primary side effect is tachycardia • 20 mg by nebulizer
  56. 56. 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.
  57. 57. 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.
  58. 58. Sodium bicarbonate • Doesn’t lower the potassium • Does lower ionized calcium
  59. 59. 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.
  60. 60. bicarbonate may cause harm • Increasing pH will decrease the ionized calcium, predisposing to hyperkalemia induced arrhythmia
  61. 61. Remove potassium • Loop diuretics and saline • Sodium polystyrene sulfonate • Dialysis
  62. 62. Dialysis Two hours on a 11:00 pm one K bath
  63. 63. 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
  64. 64. 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)
  65. 65. • 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)
  66. 66. CKD washout 2 weeks Randomize
  67. 67. 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
  68. 68. 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
  69. 69. 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
  70. 70. 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.
  71. 71. • 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
  72. 72. • 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
  73. 73. • 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)
  74. 74. • Change in potassium following the 35 mmol challenge predicted the change in potassium following 1 week on combination therapy
  75. 75. 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

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