Severe hyperkalemia with minimal electrocardiographic manifestations

Journal of Electrocardiology Vol. 32 No. 1 1999

Severe Hyperkalemia With Minimal Electrocardiographic Manifestations A Report of Seven Cases

Alberto Martinez-Vea, MD, Alfredo Bardajf, MD, Carmen Garcia, MD, and Jesus Angel Oliver, MD

Abstract: Severe hyperkalemia with minimal or nonspecific electrocardio-

graphic (ECG) changes is unusual. We report data on seven patients with renal failure, metabolic acidosis, and severe hyperkalemia (K + -> 8 mmol/L) without typical ECG changes. Initial ECGs revealed sinus rhythm and PR and QT intervals in the normal range. QRS intervals were slightly prolonged in two patients (110 ms), and incomplete right bundle branch block was evident in one. Thus, the absence of typical ECG changes does not preclude severe hyperkalemia. Key words: hyperkalemia, electrocardiogram.

Experimental and h u m a n studies have d e m o n strated that a gradual increase in serum potassium levels is followed by progressively severe electrophysiologic derangements in cardiac impulse generation and conduction. Hyperkalemia causes a decrease in the t r a n s m e m b r a n e potassium gradient, leading to a decrease in the resting m e m b r a n e potential, a decrease in the velocity of phase 0 of the action potential, and consequently a slowing of conduction. Concomitantly, t r a n s m e m b r a n e potassium permeability is increased, raising the velocity of phase 3 of the action potential and shortening the action potential as a whole (1-3). These electrophysiologic effects are reflected in the classic predictable electrocardiographic (ECG) manifestations of hyperkalemia, including tenting of the T

waves, widening of the QRS complex, loss of P waves, and eventually a sine wave pattern followed by asystole. The ECG has, therefore, b e e n considered as a sensitive indicator of hyperkalemia (4) and becomes a better predictor as the severity of hyperkalemia increases (5,6). Serum potassium levels higher t h a n 8 m m o l / L are almost invariably associated with ECG abnormalities. Nevertheless, minimal ECG changes have b e e n observed in some cases of p r o f o u n d hyperkalemia, and there have b e e n prior reports of severe hyperkalemia w i t h o u t the expected ECG findings (7). This artide describes seven cases of severe hyperkalemia (K + --> 8 mmol/L) in which the ECGs revealed minimal ECG changes and none of the abnormalities usuaJly associated with this condition. Factors that may potentially explain the lack of ECG changes despite severe hyperkalemia are reviewed.

From the Nephrology Service and Cardiology Section, Hospital Universitario de Tarragona Joan XXIII, Department of Medicine and Surgery, University Rovira i Virgili, Tarragona, Spain. Reprint requests: Alberto Martimez-Vea, MD, Apartado de Correos 12, 43080 Tarragona, Spain. Copyright © 1999 by Churchill Livingstone ® 0022-0736/99/3201-0006510.0010

Subjects During the period from J a n u a r y 1988 t h r o u g h May 1997, we identified seven patients admitted to 45

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Journal of Electrocardiology Vol. 32 No. 1 January 1999

the hospital w h o presented with severe hyperkalemia w i t h o u t the typical ECG manifestations. Clinical and laboratory data including serum sodium, potassium, bicarbonate, urea, creatinine and calcium concentrations, and ECGs were retrospectively reviewed. Severe hyperkalemia was defined as a serum potassium concentration of 8 m m o l / L or more. In all patients, repeated determinations of serum potassium confirming the initial values were required. Blood specimens were not h e m o l y z e d and were obtained w i t h o u t mechanical difficulty or prolonged ischemia and within 1 h o u r of the performance of the ECG in every case. No therapy was initiated b e t w e e n the performance of the ECG and blood drawing in a n y of the patients. White blood cell and platelet counts were all in the n o r m a l range. All ECGs were read by one of the a u t h o r s (A.B.). Cardiac r h y t h m , QRS axis, PR a n d QT intervals, w i d t h of QRS complex, m o r p h o l o g y of P a n d T waves, QRS complex, a n d ST s e g m e n t were evaluated. The presence of b u n d l e b r a n c h block a n d left v e n t r i c u l a r h y p e r t r o p h y (8) w e r e also analyzed.

Results Clinical and laboratory data of patients are s h o w n in Table 1. M e a n serum levels of potassium were 8.2 m m o l / L (range 8 - 8 . 4 ) . Metabolic acidosis was present in all cases; slight h y p o n a t r e m i a was observed in one patient, and hypocalcemia in four. H y p e r k a l e m i a a p p e a r e d in the setting of acute renal failure in four patients, a n d was related to a c h r o n i c renal failure in the r e m a i n i n g three. C o n c o m i t a n t a n g i o t e n s i n - c o n v e r t i n g e n z y m e inhibitor t h e r a p y c o n t r i b u t e d to h y p e r k a l e m i a in t w o cases. Table 2 s u m m a r i z e s the ECG data. All patients w e r e in regular sinus r h y t h m . PR a n d QT intervals w e r e in the n o r m a l range. The d u r a t i o n of the QRS c o m p l e x was slightly p r o l o n g e d in two patients (1 10 ms) a n d an i n c o m p l e t e right b u n d l e b r a n c h block was evident in one; r e p e a t e d ECGs s h o w e d that this a b n o r m a l i t y persisted despite the correction of the h y p e r k a l e m i a . QRS m o r p h o l o g y was n o r m a l in five patients; a small q w a v e was observed in two. Five patients h a d a small negative T w a v e in I a n d aVL leads. Criteria

Table 1. Clinical and Laboratory Data

Serum Serum Serum Serum Serum Sodium Potassium Creatinine Bicarbonate Calcium (retool/L) (mmol/L) (/~mol/L) (mmol/L) (mmoI/L)

Patient

Age/ Sex

Etiology of Hyperkalemia

1

40/F

138

8.2

2

29/F

CRF-HD (dietetic transgression) CRF

144

3

58/M

4

73/M

5

56/F

6

73/F

CRF-Iz[D (dietetic transgression ARF (hypovolemia + ACEI) ARF (UTO: cancer of cervix) ARE (myeloma)

7

53/F

ARF (UTO: NonHodgkin's lymphoma)

915

19.2

nd

8

1471

7.3

2.59

135

8

953

nd

nd

i37

8.1

634

15.4

137

8.6

2120

138

8.i

131

8.4

Initial Treatment

Serum Potassium After Treatment (retool/L)

HD

ND

Glucose, insulin, salbutamol, sodium bicarbonate

6.3

HD

ND

2.04

Salbutamol

7.5

16.1

nd

Salbutamol

7.8

2136

13.4

2.25

ND

1060

11

2.35

Glucose, insulin, sodium bicarbonate Glucose, insulin, sodium bicarbonate

7.7

CRF-HD, chronic renal failure on hemodialysis; ARF, acute renal failure; ND, not determined; ACEI, angiotensin-converting enzyme inhibitor therapy; UTO, urinary tract obstruction; HD, hemodialysis; M, male; F, female.

Hyperkalemia and the ECG

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Martinez-Vea et al.

47

Table 2. E C G D a t a QRS Axis

PR (ms)

QRS (ms)

QTc (ms)

P Morphology

60

-40 °

I80

110

480

Normal

Sinus Sinus

120 53

30 ° 0°

160 180

80 110

450 495

4

Sinus

100

-30 °

120

80

5

Sinus

85

45 °

140

6

Sinus

102

-20 °

7

Sinus

104

30 °

Patient

Rhythm

1

Sinus

2 3

HR (bpm)

QRS Morphology

ST Morphology

T Morphology

Normal

Normal

Normal Normal

Normal Normal

Normal Normal

380

Normal

Normal

Normal

80

430

Normal

Normal

Normal

130

90

435

Notched

Normal

160

80

370

Normal

Small q waves in I and aVL Small q waves in II, III, and aVF

Negative in and aVL Normal Negative in and aVL Negative in and aVL Negative in and aVL Negative in aVL Normal

Normal

BBB

LVH

I

No

Yes

I

No Yes

No No

I

No

No

I

No

No

No

No

No

No

HR, heart rate; BBB, bundle b r a n c h block; LVFI, left ventricular hypertrophy; QTc, QT corrected.

for left ventricular hypertrophy were met in only one patient. Selected Case Histories Case 2. A 29-year-old woman was admitted with a 1-week history of fatigue, nausea, vomiting, hematemesis, and melena. Her medical history included postmeningitic mental retardation and chronic renal failure of u n k n o w n origin. Laboratory analysis revealed serum sodium, 144 rumor/L; potassium, 8 retool/L; bicarbonate 7.3 retool/L; calcium, 2.5 retool/L; creatinine, 1471 /~mol/L; blood urea, 90 retool/L; and glucose, 5.2 mmol/L. Arterial blood gas determination (on room air) revealed pH, 7.16; oxygen partial pressure, 104 mmHg; and carbon dioxide partial pressure, 20 mmHg. The hemoglobin and hematocrit were 8.1 g/dL and 25.5%, respectively. The ECG (Fig. 1)

I]

Fig. 1. Case 2. ECG showing sinus tachycardia and normal repolarization in a patient with serum potassium of 8 mmol/L.

......'4.-~ -'.4J'~

,-g-"~--g~,-Q.

riga DEI~|TMO:

OCOO[-GO00

showed sinus tachycardia. P, QRS, ST-segment and T morphology, PR and QT-corrected interval, and QRS duration were all normal (Table 2). After treatment with sodium bicarbonate, glucose, insulin, and salbutamol, serum potassium decreased to 6.3 mmol/L. Hemodialysis was suggested, but it was refused by the family. The patient died 8 hours after admission. Case 4. A 73-year-old man was admitted with a 5-day history of nausea and diarrhea. His medical history included chronic pancreatitis, hypertension, mild renal insuffidency, and myocardial hypertrophy with systolic dysfunction. Previous medication cons~sted of captopril, hydrochlorothiazide, and amiloride. Clinical signs of hypovolemia were evident. Laboratory analysis revealed serum sodium, 137 retool/L; potassium, 8.1 retool/L; bicarbonate, 15.4 retool/L; calcium, 2.04 retool/L; creatinine, 634

48

Journal of Electrocardiology Vol. 32 No. 1 January 1999 L~

!E

-.,,,

Fig. 2. Case 4. ECG showing sinus tachycardia and a negative T wave in I and aVL in a patient with serum potassium of 8.1 mmol/L.

; .... m~ ~/[t[

;~¢

!ii:F!})~

~L

,:-nu

/zmol/L; blood urea, 56 mmol/L; and glucose, 7 mmol/L. Arterial blood gas determination (on r o o m air) revealed pH, 7.29; oxygen partial pressure, 94 mmHg; and carbon dioxide partial pressure, 31.4 mmHg. The hemoglobin and hematocrit were 11 gldL and 32.5%, respectively. The ECG (Fig. 2) showed sinus tachycardia. P, QRS, and ST-segment mm~hology, PR and QT-corrected interval, and QRS duration were all n o r m a l (Table 2). A negative T wave in I and aVL was observed. The etiology of the hyperkalemia was believed to be the acute renal failure due to gastrointestinal fluid loss associated with captopril and amiloride therapy. After administration of salbutamol, serum potassium decreased to 7.5 mmol/L. Over the n e x t 48 hours, he was treated with calcium polystyrene sulphonate and isotonic saline solution; serum potassium r e t u r n e d to normal, and serum creatinine concentration also r e t u r n e d to its usual baseline value of 259/zmol/L.

Discussion These cases demonstrate that severe hyperkalemia can be seen without the typical ECG manifestations. In our patients, hemolysis and thrombocytosis were not present in the blood specimens, and there was no prolonged muscle ischemia during venipuncture. Furthermore, serum potassium remained particularly high even after initial insulin, salbutamol, and/or bicarbonate therapy. Thus, it seems very improbable that the lack of ECG changes was related to a spurious hyperkalemia in any of our patients. Experimental hyperkalemia and several retrospective h u m a n studies have demonstrated a close

correlation b e t w e e n serum potassium concentrations and ECG effects. These studies report a predictable sequence of ECG changes with increasing hyperkalemia, usually seen w h e n serum potassium exceeds 6.5 to 6.7 m m o l / L (5,6). Some investigators did not find consistent ECG changes until the serum potassium concentrations exceeded 7.6 m m o l / L (6), and it has been postulated that extremely high levels of serum potassium (K + ~ 8 retool/L) are almost always associated with the classic ECG manifestations. Nevertheless, the predictive accuracy of the ECG for hyperkalemia has recently been questioned. W r e n n et al. (9), in a study including a large n u m b e r of patients with hyperkalemia, analyzed the sensitivity and specificity of the ECG in predicting the presence and severity of the condition. The best sensitivities and specificities for predicting hyperkalemia were 0.43 and 0.86, and the sensitivity for detecting potassium levels of more t h a n 6.5 m m o l / L was also relatively poor (0.62). In that study, most of the hyperkalemic patients had serum potassium concentrations of less than 6.5 mmol/L, and the n u m b e r of patients with severe hyperkalemia (K + > 8 retool/L) was not specified. Our cases are particularly interesting because they demonstrate that an extremely high level of serum potassium is not always associated with typical ECG changes. Previous reports of severe hyperkalemia without the expected ECG findings are rare. Two w e l l - d o c u m e n t e d cases of p r o f o u n d hyperkalemia (serum potassium levels of 9.2 and 10.3 retool/L, respectively) w i t h o u t ECG changes were described by Szerlig e t a ] . (7). Currens and Crawford (10) described a case of severe hyperka]emia (K + = 12.7 mmol/L) w i t h o u t the expected ECG changes; however, there is some uncertainty

Hyperkalemia and the ECG

a b o u t the interpretation of this case, and spurious h y p e r k a l e m i a could not be ruled out completely. Atypical or nonspedfic ECG changes have also been observed in cases of profound hyperkalemia. Hylander (11) reports a case of extreme hyperkalemia (K + = 10.1 mmol/L) with an ECG showing widened QRS complexes mimicking a bundle branch blod~. A type I (Wenckebach) second-degree sinoatrial exit block has been described by Yu (12) in a patient with a serum potassium concentration of 11 mmol/L. Several potential explanatory factors for the lack of ECG changes in severe hyperkalemia have b e e n proposed. Baseline ECG changes such as left ventricular hypertrophy, intraventricular conduction delay, and m y o cardial ischemia m a y all m a s k ECG manifestations of hyperkalemia (1). Two of our patients had a left ventricular h y p e r t r o p h y or a bundle branch block, which m a y have modified the typical ECG changes associated with the condition. Electrolyte abnormalities m a y also modify the m y o cardial sensitivity to potassium. Addosis, hypoxia, hyponatremia, and hypocalcemia m a y all increase myocardial sensitivity to hyperkalemia (4, 5), whereas hypercalcemia and hypernatremia m a y minimize or eliminate the effect of hyperkalemia on the heart (1,2,13). Hypernatremia was not present in any of our patients, and hypercalcemia was not evident in the patients in w h o m serum calcium concentrations were recorded. One notable finding in our patients was the absence of ECG manifestations of hyperkalemia despite the presence of severe metabolic acidosis. Acidosis m a y increase myocardial sensitivity to potassium and m a y also produce tall, peaked T waves in the absence of hyperkalemia (14). Finally, the rate of increase in s e r u m p o t a s s i u m m a y influence the d e v e l o p m e n t of ECG changes (3,15). Rapid increases in p o t a s s i u m concentrations m a y potentiate the cardiotoxic effects of h y p e r k a lemia, w h e r e a s if h y p e r k a l e m i a develops slowly (eg, chronic renal failure), cardiac manifestations m a y be attenuated. Chronic renal failure was present in three of o u r patients a n d m a y explain the lack of ECG changes in these cases. However, no obvious e x p l a n a t i o n can be p r o p o s e d w i t h regard to our four patients in w h o m h y p e r k a l e m i a a p p e a r e d in the setting of acute renal failure. In conclusion, our cases confirm the lack of correlation b e t w e e n severe h y p e r k a l e m i a and diagnostic ECG changes, Clinicians should be aware that the ECG is not always a reliable indicator of severe h y p e r k a l e m i a because life-threatening elevations of s e r u m p o t a s s i u m levels are s o m e t i m e s seen in the absence of the typical ECG changes.

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Martinez-Vea et al.

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Editor's N o t e : There was a consensus a m o n g the reviewers a n d two ad hoc consultants that "minimal" ECG changes in the presence of "crisis" levels of s e r u m p o t a s s i u m (K + >- 8 m m o l / L ) was m o s t unusual. Indeed, one expert stated, "In the 40 some years of interest in the clinical a n d laboratory aspects of potassium, I h a v e yet to see a K + over 8 w i t h o u t telltale signs of h y p e r k a l e m i a (in m a n ) . " The editor's office w o u l d w e l c o m e letters to the editor s u m m a r i z i n g y o u r experience in response to the interesting findings in this report of MartinezVea a n d coworkers.

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