Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia in haemodialysis patients

Shakil Aslam, Eli A. Friedman and Onyekachi Ifudu

Renal Disease Division, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York, USA



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. It is speculated, but unconfirmed, that the usual electrocardiographic manifestations of hyperkalaemia are less frequent and less pronounced in persons with end-stage renal disease (ESRD) than in those with normal renal function. We studied 74 consecutively selected stable haemodialysis patients to determine the prevalence of electrocardiographic changes of hyperkalaemia in stable persons with ESRD receiving haemodialysis.

Methods. Pre-dialysis serum potassium concentration and other electrolytes were measured and simultaneous 12-lead electrocardiogram obtained.

Results. The 74 study subjects (45 men, 29 women) comprised 63 blacks (85%), four Hispanics (6%), four whites (6%), and three Asians (4%) of mean±standard deviation age 55.5±14.7 years. Mean pre-dialysis potassium concentration was 4.9±0.71 mEq/l (range 3.3–6.7). No study subject evinced arrhythmia or any of the typical electrocardiographic changes associated with hyperkalaemia. There was no significant difference in T wave amplitude (F statistic=2.1; P=0.11) or T wave to R wave ratio (F statistic=2; P=0.12) between quartiles of serum potassium concentration. Also, T wave amplitude was equivalent in patients with serum potassium concentration >5.5 mEq/l (7.1±4.1 mm) or <=5.5 mEq/l (5.2±3.5 mm) (P=0.13). Linear regression analysis showed that the total serum calcium concentration had an inverse relation with T wave amplitude (P=0.03) after adjustment for other factors (a high total serum calcium concentration was associated with a low T wave amplitude).

Conclusion. Haemodialysis patients with hyperkalaemia may not exhibit the usual electrocardiographic sequella of hyperkalaemia, possibly due in part to fluctuations in serum calcium concentration. Thus, the absence of electrocardiographic changes in hyperkalaemic haemodialysis patients should be interpreted with caution.

Keywords: arrythmia; calcium; chronic renal failure; ECG; ESRD; haemodialysis; hyperkalaemia; potassium; T wave



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
There is incomplete understanding of the electrophysiologic consequences of fluctuations in potassium concentration in end-stage renal disease (ESRD). However, it has been postulated that patients with ESRD have a tolerance for hyperkalaemia, and that the usual cardiac and neuromuscular sequella of hyperkalaemia are less evident in ESRD patients than in those with normal renal function [14].

Ascertaining whether electrocardiography (ECG) is a reliable tool to detect potentially lethal hyperkalaemia in haemodialysis patients is critical, because the course of immediate care proffered by clinicians in non-renal failure patients with hyperkalaemia is guided by the presence or absence of the ECG changes associated with hyperkalaemia, such as a tall peaked T wave.

Moreover, relying on symptoms of hyperkalaemia may not be helpful in determining whether hyperkalaemia is life threatening in ESRD. The most prominent adverse effects of hyperkalaemia are unpredictable and potentially lethal arrhythmias, respiratory depression, and weakness [5,6]. But, weakness in a haemodialysis patient may result from myriad other reasons and would not necessarily be primarily attributed to hyperkalaemia.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
We studied 74 consecutively selected stable patients with ESRD receiving haemodialysis in an outpatient dialysis facility in Brooklyn, New York. Patients were selected from a pool of 136 patients with ESRD. Inclusion criteria were: ESRD on maintenance haemodialysis thrice weekly for at least 3 months, age 18 years and over, and patient consent. Exclusion criteria were: age less than 18 years, patient refusal, and treatment with drugs known to affect cardiac conduction. The following information was obtained from each patient: age, gender, race, aetiology of ESRD, and duration of ESRD.

Serum potassium concentration, total serum calcium concentration, serum sodium concentration, and serum bicarbonate concentration were measured in a blood sample obtained immediately before a regular dialysis treatment. Laboratory measurement of serum electrolytes was performed in the central hospital laboratory within 1 h after blood drawing. A simultaneous 12-lead ECG was obtained in all subjects, by one investigator (S.A.). All ECGs were read by one investigator without knowledge of the serum potassium concentration. The same investigator also measured the pre-cordial lead T wave amplitude and calculated the T wave to R wave ratio for each patient.

Conventional dialysis was performed using modified cellulose acetate hollow-fibre dialyzers (Althin Medical Inc., Miami Lakes, FL, USA), a bicarbonate-based dialysate with sodium concentration of 140 mEq/l for 4 h thrice weekly.

Statistical analysis
The serum potassium concentration was sorted into quartiles and analysis of variance was used for between group comparisons of mean T wave amplitude and the T wave to R wave ratio. Tukey tests were used to test for differences between individual means. Multiple regression analysis was used to assess the independent association of T wave amplitude (outcome variable) with all other measured variables. Independent variables were age, duration of ESRD, pre-dialysis serum bicarbonate concentration, total serum calcium concentration, serum sodium concentration, and serum potassium concentration (<=5.5 vs >5.5 mEq/l). Multiple regression results include Beta, the standardized regression coefficient, and the standard error (SE). All P values are two-tailed. Plus/minus values are mean± standard deviation (SD). Computations were done in SPSS [7] (Statistics Program for Social Sciences version 8.0, 1997, SPSS Inc., Chicago, IL, USA).



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The 74 study subjects (45 men, 29 women) comprised 63 blacks (85%), four Hispanics (6%), four whites (6%), and three Asians (4%) of mean±SD age 55.5±14.7 years (range 24–83). Mean duration of ESRD was 27±23 months (range 4–84). Of the cohort, 34 (45%) had diabetes mellitus. Mean pre-dialysis serum potassium concentration was 4.9±0.71 mEq/l (range 3.3–6.7). Mean pre-cordial lead T wave amplitude for the entire group was 5.1±4.1 mm and the mean T wave to R wave ratio was 0.3±0.1 mm.

Mean serum total calcium concentration was 9.1±0.94 mg/dl (range 7.5–11.6), mean serum sodium concentration was 137±3.2 mEq/l (range 130–143), and mean serum bicarbonate concentration was 22±3 mEq/l (range 10–28).

No study subject evinced arrhythmia or any of the typical ECG changes associated with hyperkalaemia. There was no significant difference in T wave amplitude (F statistic=2.1; P=0.11) or T wave to R wave ratio (F statistic=2; P=0.12) between quartiles of serum potassium concentration (Table 1Go). T wave amplitude was equivalent in patients with serum potassium concentration >5.5 (7.1±4.1) or <=5.5 mEq/l (5.2±3.5 mm) (P=0.13). Also, T wave to R wave ratio was equivalent in patients with serum potassium concentration >5.5 (2.8±3) or <=5.5 mEq/l (1.9±2.7 mm) (P=0.37). Bivariate correlation analysis showed that the r value for the inverse correlation between serum calcium concentration and T wave amplitude was -0.32 (P=0.007; Figure 1Go). Multiple linear regression analysis showed that total serum calcium concentration had an inverse relation with T wave amplitude (P=0.03) after adjustment for other factors (a high total serum calcium concentration was associated with a low T wave amplitude) (Table 2Go).


View this table:
[in this window]
[in a new window]
 
Table 1.  Comparison of T wave amplitude and T wave to R wave ratio by quartile of serum potassium (K) concentration

 


View larger version (19K):
[in this window]
[in a new window]
 
Fig. 1.  Relation between ECG T-wave amplitude and pre-dialysis serum calcium level in haemodialysis patients.

 

View this table:
[in this window]
[in a new window]
 
Table 2.  Results of multiple linear regression analysis with T wave amplitude as the outcome variable

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
We found that haemodialysis patients with a high pre-dialysis serum potassium concentration (>5.5 mEq/l) did not manifest typical ECG changes associated with hyperkalaemia and that total serum calcium concentration had an inverse relation with T wave amplitude. Also, there was no difference in T wave amplitude or T wave to R wave ratio between those with low or high pre-dialysis serum potassium concentration.

Our results confirm and extend the findings of a case report by Szerlip et al. [1], of two renal failure patients with a serum potassium concentration >9 mEq/l who did not have ECG manifestations. Hyperkalaemia reduces the resting membrane potential, bringing it closer to threshold. It slows conduction velocity and increases the rate of repolarization due to increased membrane permeability for potassium [5]. As such, changes in repolarization that may manifest initially as tall peaked T waves in the pre-cordial leads of the ECG are early signs of hyperkalaemia [6]. Tall peaked T waves may be followed by decreased amplitude of the R wave, widened QRS complex, prolonged P–R interval, and then decreased amplitude and disappearance of the P wave [6]. Finally, the QRS blends into the T wave, forming the classic sine wave [6]. Cardiac arrest or ventricular arrhythmia may occur at any point in this progression.

Once the typical ECG changes are detected in a person with hyperkalaemia, the immediate course of action is the administration of intravenous calcium gluconate. Calcium antagonizes the effect of hyperkalaemia on the membrane by reducing the threshold potential, thereby restoring the normal difference between the two potentials that is necessary for excitability.

We do not have a validated explanation for the absence of usual ECG findings of hyperkalaemia in ESRD. However, our finding of an inverse relation between total serum calcium concentration and T wave amplitude suggests that elevated serum calcium concentration in haemodialysis patients may blunt the cardiotoxic effects of hyperkalaemia [8]. Although secondary hyperparathyroidism, a common feature of ESRD, is usually associated with hypocalcaemia, total serum calcium levels in many haemodialysis patients is often above the average due to a regimen designed to increase serum calcium concentration and combat secondary hyperparathyroidism [9]—oral calcium therapy, supplemental vitamin D, and treatment with a dialysate that often has as much as 3.5 mEq/l of ionized calcium.

Furthermore, while total body potassium is decreased in haemodialysis patients [10,11], elevated serum potassium concentration tells little about the ratio between intracellular and extracellular potassium, which is the critical factor in membrane depolarization. Complex electrolyte perturbations impinge on the stability of myocardial cells in partially corrected uraemia including fluctuations in calcium, magnesium, and pH, any of which may alter expression of hyperkalaemia.

It is also possible that cell membrane changes in ESRD, such as deposition of phospholipids may counteract any of the cardiac effects of hyperkalaemia. In addition, it is suggested that the rate of rise in serum potassium, which is slow in ESRD, may be more relevant than the actual level of serum potassium attained [12]. Thus, during a slow rise in serum potassium concentration, concurrent compensatory changes occur to counteract the effect of hyperkalaemia on membrane depolarization.

A limitation of our study is that we did not compare the study ECG to prior ECGs when patients were not hyperkalaemic and we did not measure ionized serum calcium. We acknowledge that as non-specific ECG changes including ischaemic-appearing changes of uncertain significance are common in the dialysis population [13,14], these may obscure the usual changes of hyperkalaemia.

Many ESRD patients receive concomitant care from generalist physicians and nephrologists. It should be recognized that the distribution of pre-dialysis serum potassium values in ESRD is different from that in health [2,15], with a mean and distribution curve shifted to the right (higher baseline potassium values). The majority of patients on haemodialysis have pre-dialysis serum potassium concentration >5 mEq/l [2,15], the upper limit of normal in persons without ESRD. In fact, as many as 19% of patients receiving haemodialysis may have pre-dialysis serum potassium values >6 mEq/l [2]. Therefore, an elevated serum potassium concentration in ESRD patients is bound to be frequently encountered by non-nephrologists or emergency room physicians when evaluating these patients for non-renal medical problems. We emphasize that despite the absence of ECG changes of hyperkalaemia in ESRD, hyperkalaemia is still a potentially life-threatening condition in ESRD [16]. In three haemodialysis patients whose deaths were attributed to hyperkalaemia by Siddiqui et al. [16], the serum potassium concentration was 8, 7.4, and 7.8 mEq/l, respectively, just before cardiac arrest. On the other hand, the two patients in the report by Szerlip et al. [1], with serum potassium concentrations of 9.2 and 10.2 mEq/l, respectively, did not manifest any specific symptom or ECG feature of hyperkalaemia. Thus, the conundrum, in the absence of ECG changes to guide therapy, the threshold serum potassium concentration that should trigger immediate potassium lowering measures or use of intravenous calcium gluconate in persons with ESRD is unclear.

Lacking any supportive scientific data, a common-sense approach to deciding what to in ESRD patients with ‘elevated serum potassium’ without ECG changes would be to compare the value with the patient's ‘usual’ serum potassium concentration and also take their general clinical condition into consideration. When uncertain of the importance of a raised potassium level, it is prudent to go ahead and administer calcium gluconate, as the downside risk is minimal.

Clearly, extrapolating usual ECG changes of hyperkalaemia in non-renal failure patients to persons with ESRD is an unreliable means of detecting potentially lethal hyperkalaemia. Thus, the absence of ECG changes in hyperkalaemic haemodialysis patients should be interpreted with caution.



   Notes
 
Correspondence and offprint requests to: Onyekachi Ifudu, Renal Disease Division, Box 52, Department of Medicine, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, NY 11203, USA. Email: oifudu{at}downstate.edu Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Szerlip HM, Weiss J, Singer I. Profound hyperkalemia without electrocardiographic manifestations. Am J Kidney Dis1986; 7: 461–465[ISI][Medline]
  2. Tzamaloukas AH, Avasthi PS. Temporal profile of serum potassium concentration in nondiabetic and diabetic outpatients on chronic dialysis. Am J Nephrol1987; 7: 101–109[ISI][Medline]
  3. Papadimitriou M, Roy RR, Varkarakis M. Electrocardiographic changes and plasma potassium levels in patients on regular haemodialysis. Br Med J1970; 2: 268–269[ISI]
  4. Frohnert PP, Giuliani ER, Friedberg M, Johnson WJ, Tauxe WN. Statistical investigation of correlations between serum potassium levels and electrocardiographic findings in patients on intermittent hemodialysis therapy. Circulation1970; 41: 667–676[ISI][Medline]
  5. Greenspan K, Wunsch C, Fisch T. T wave of normo- and hyperkalemic canine heart: effect of vagal stimulation. Am J Physiol1965; 208: 954–960[Abstract/Free Full Text]
  6. Fisch C. Relation of electrolyte disturbances to cardiac arrhythmia. Circulation1973; 47: 408–419[ISI][Medline]
  7. Norusis MJ. SPSS for Windows Advanced Statistics, Release 8.0 SPSS Chicago, IL, 1997
  8. Ettinger PO, Regan TS, Olderwurtel HA. Hyperkalemia, cardiac conduction, and the electrocardiogram: overview. Am Heart J1974; 88: 360–371[ISI][Medline]
  9. Salem MM. Hyperparathyroidism in the hemodialysis population: a survey of 612 patients. Am J Kidney Dis1997; 29: 862–865[ISI][Medline]
  10. Oh MS, Levinson SP, Carroll HJ. Content and distribution of water and electrolytes in maintenance hemodialysis. Nephron1975; 14: 421–432[ISI][Medline]
  11. Boddy K, King PC, Lindsay RM et al. Total body potassium in non-dialysed and dialysed patients with chronic renal failure. Br Med J1972; 1: 771–775[Medline]
  12. Surawicz B, Chlebus H, Muzzoleni A. Hemodynamic and electrocardiographic effects of hyperpotassemia. Differences in response to slow and rapid increases in concentration of plasma K. Am Heart J1967; 73: 647–664[ISI][Medline]
  13. Shapira OM, Bar-Khayim Y. ECG changes and cardiac arrhythmias in chronic renal failure patients on hemodialysis. J Electrocardiol1992; 25: 273–279[ISI][Medline]
  14. Abe S, Yoshizawa M, Nakanishi N, Yazawa T, Yokota K, Honda M, Sloman G. Electrocardiographic abnormalities in patients receiving hemodialysis. Am Heart J1996; 131: 1137–1144[ISI][Medline]
  15. O'Kell RT, Elliott JR. Serum potassium values in adults. Am J Med Tech1974; 40: 120–124[ISI][Medline]
  16. Siddiqui JY, Fitz AE, Lawton RL, Kirkendall WM. Causes of death in patients receiving long-term hemodialysis. J Am Med Assoc1970; 212: 1350–1354[Medline]
Received for publication: 11. 8.01
Accepted in revised form: 8. 4.02





This Article
Abstract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (2)
Disclaimer
Request Permissions
Google Scholar
Articles by Aslam, S.
Articles by Ifudu, O.
PubMed
PubMed Citation
Articles by Aslam, S.
Articles by Ifudu, O.