Basic and Bedside Electrocardiography, 1st Edition (2009)

Chapter 25. Electrolyte Abnormalities


·   Among the various electrolyte abnormalities, hyperkalemia, hypokalemia, hypercalcemia, and hypocalcemia are the only disorders that can cause reliable diagnostic changes in the electrocardiogram (ECG). These ECG changes can be recognized well before the results of the laboratory tests become available. The severity of these electrolyte abnormalities usually parallels the changes in the ECG.

·   A simple rule to remember regarding the effect of these electrolyte abnormalities on the ECG is that when increased levels are present (hyperkalemia or hypercalcemia), the QT interval is shortened. Inversely, when decreased levels of these electrolytes are present (hypokalemia or hypocalcemia), the QT interval is prolonged. Figure 25.1 shows the ECG abnormalities associated with each of these electrolyte disorders.

·   The normal level of serum potassium varies from 3.3 to 5.3 millimoles per liter (mmol/L), also expressed as milliequivalents per liter (mEq/L). Hyperkalemia implies the presence of higher than normal levels of serum potassium.

Figure 25.1: Electrolyte Abnormalities. Only disorders of potassium and calcium can be reliably diagnosed in the electrocardiogram. When the serum level of these electrolytes is increased (hyperkalemia and hypercalcemia), the QT interval is shortened, whereas when the serum level is low (hypokalemia and hypocalcemia), the QT interval is prolonged.

·   Among the electrolyte disorders, hyperkalemia is the most fatal. It also exhibits the most remarkable changes in the ECG. The ECG abnormalities generally reflect the increasing severity of the hyperkalemia, thus the ECG is useful not only in the diagnosis of this electrolyte disorder, but is also helpful in determining the intensity in which hyperkalemia should be treated.

·   Figure 25.2 is a diagrammatic representation of the ECG changes associated with increasing levels of potassium in the serum.

o    Mild hyperkalemia (<6.0 mmol/L): Peaking of the T waves occurs and may be the earliest and only abnormality that can be recognized. The QT interval is normal or shortened (Fig. 25.2B).

o    Moderate hyperkalemia (6.0 to 7.0 mmol/L): More pronounced peaking of the T waves occur, QRS complexes widen, P waves become broader with diminished amplitude, and PR interval lengthens resulting in atrioventricular (AV) block (Fig. 25.2C).

Figure 25.2: The Electrocardiogram of Hyperkalemia. Diagram depicts the electrocardiogram changes as the level of hyperkalemia increases. (A) Normal, (B) mild to moderate hyperkalemia, (C) moderate, and (D) severe hyperkalemia.

o    Severe hyperkalemia (>7.0 mmol/L): P waves become unrecognizable, further widening of the QRS complex occurs, S and T waves merge with a very short ST segment resulting in a sinusoidal wave, ST segment may be elevated in V1-2 and mistaken for acute ischemic injury, and, finally, slowing of the heart rate, asystole, or ventricular flutter can occur (Fig. 25.2D).

·   Mild hyperkalemia (<6.0 mmol/L): Peaking of the T waves is the earliest to occur and is the most characteristic ECG pattern of hyperkalemia. Hyperkalemic T waves are often described as “tented” because they closely resemble the shape of a tent. The T waves are tall and symmetrical with a pointed tip and a narrow base (Fig. 25.3,25.4,25.5). The QT interval is generally short, unless coexisting abnormalities such as hypocalcemia or myocardial disease are present.

·   Moderate hyperkalemia (6.0 to 7.0 mmol/L): As the level of serum potassium increases, the amplitude of the T wave also increases and often the height of the T wave becomes taller than the R wave. The T waves are tallest in precordial leads V2-4, because of the proximity of these leads to the myocardium (Figs. 25.5,25.6,25.7).

Figure 25.3: “Tented” T waves. the most distinctive abnormality in hyperkalemia is the presence of tented T waves characterized by tall, peaked, and symmetrical t waves with a narrow base and short QT interval. in the above example, the QT interval measures 0.34 seconds.

·   The onset of the P wave and QRS abnormalities is more difficult to predict than the T wave changes. In general, the P waves and QRS complexes start to widen when moderate hyperkalemia is present, as conduction through the atria and ventricles becomes delayed (Fig. 25.7).

·   Severe hyperkalemia (>7.0 mmol/L): When the potassium level increases to >7.0 mmol/L, the amplitude of the P wave decreases until the P waves are no longer detectable. The absence of P waves in spite of normal sinus rhythm is due to marked slowing of the sinus impulse across the atria or the sinus impulse traveling through specialized internodal pathways. Sinoventricular rhythm is the term used to describe sinus rhythm without any discernible P waves. Sinoventricular rhythm is impossible to distinguish from junctional rhythm when the QRS complexes are narrow or from accelerated ventricular rhythm when the QRS complexes are wide.

·   Other ECG changes associated with severe hyperkalemia are shown in Figs. 25.7,25.8,25.9,25.10,25.11,25.12,25.13,25.14,25.15:

o    Further widening of the QRS complex, shortening of the ST segment and fusion of the S wave with the T wave resembling a sine wave (Figs. 25.7, 25.12, and 25.13).

o    P waves completely disappear in spite of the rhythm being normal sinus, resulting in sinoventricular rhythm (Figs. 25.8, 25.10,25.11,25.12,25.13,25.14,25.15).

o    ST segment elevation mimicking acute ischemic injury can occur, especially in the right sided precordial leads V1-2 (Fig. 25.9).

o    Severe bradycardia (Figs. 25.10,25.11,25.12,25.13,25.14,25.15) or ventricular flutter/fibrillation may occur.

·   Figures 25.11,25.12,25.13 are from the same patient showing increasing levels of potassium.

·   Figures 25.14 and 25.15 show very high potassium levels, which can lead to cardiac arrest.

Figure 25.4: Mild Hyperkalemia. The most significant electrocardiogram finding of mild hyperkalemia is the presence of peaked T waves in virtually all leads with upright T waves as shown.

Figure 25.5: Moderate Hyperkalemia. Potassium level is 6.6 mmol/L. Peaking of the T waves (arrows) is noted diffusely. The T waves are tented with a pointed tip and a narrow base. The T waves measure 10 mm in V3 and are taller than the QRS complexes.

Figure 25.6: Wide QRS Complex. (A) Before therapy, the potassium level is 6.6 mmol/L. The QRS complexes in the precordial leads are wide measuring 124 milliseconds. The R waves are upright in V1 (arrows). (B) Posttherapy, potassium level is 4.6 mmol/L. The QRS complexes are narrower and the tall R waves in V1 are no longer present (arrows). ms, milliseconds.


Figure 25.7: Severe Hyperkalemia with Widening of the QRS Complexes. Potassium level is 7.6 mmol/L. The PR interval is slightly prolonged. The QRS complexes are wide with marked peaking of the T waves. The S wave continues directly into the T wave in leads II, aVF, and V2 to V5, resembling a sine wave.

Figure 25.8: Marked Bradycardia in a Patient with Severe Hyperkalemia. Potassium level is 8.3 mmol/L. The QRS complexes are widened and are not preceded by P waves. There is marked peaking of the T waves, which is the hallmark of hyperkalemia. The rhythm is often called junctional, but is impossible to differentiate from sinoventricular rhythm, which is sinus rhythm without discernible P waves.

Figure 25.9: Severe Hyperkalemia with ST Elevation in V1V2 Resembling Acute ST Elevation Myocardial Infarction. Potassium level is 8.6 mmol/L. The T waves are markedly peaked in all leads especially V1 to V5, II, III, and aVF. The T wave in V3 measures almost 25 mm and most T waves are taller than the QRS complexes. ST segment elevation in V1-2 can be mistaken for acute myocardial infarction or the ST elevation associated with the Brugada electrocardiogram.


Figure 25.10: Absent P waves and Wide QRS Complexes in Severe Hyperkalemia. Potassium level is 9.0 mmol/L. P waves are absent and the QRS complexes are wide with a left bundle branch block configuration. The rhythm is often called sinoventricular, although this is difficult to differentiate from accelerated idioventricular rhythm.

Figure 25.11: Generalized Peaking of the T Waves is the Hallmark of Hyperkalemia. Potassium level is 8.7 mmol/L. In hyperkalemia, peaking of the T waves is generalized, occurring in almost all T waves that are upright. Note that some of the T waves are taller than the QRS complexes.

Figure 25.12: The Presence of Sine Waves Indicate that the Hyperkalemia is Severe. Potassium level is 8.9 mmol/L. Note that the sine waves are formed by the short ST segment causing the S waves to continue into the T waves. These are seen in both limb and precordial leads.


Figure 25.13: Marked Widening of the QRS Complexes Indicates More Advanced Hyperkalemia. Potassium level is >10.0 mmol/L.

ECG Findings of Hyperkalemia

·   Increased amplitude and peaking of the T waves. This is the earliest, most consistent, and most characteristic ECG abnormality associated with hyperkalemia. T-wave peaking persists and worsens with increasing levels of hyperkalemia.

·   The QT interval is short or normal.

·   As hyperkalemia worsens, the QRS complexes widen.

·   The P wave becomes broader and the amplitude becomes lower.

·   AV conduction becomes prolonged.

·   The P waves eventually disappear resulting in sinoventricular rhythm.

·   The S wave continues into the T wave resulting in a sine wave configuration.

·   Cardiac arrest from marked bradycardia, asystole, or ventricular flutter/fibrillation.

Figure 25.14: Slow Ventricular Rhythm and Unusually Wide QRS Complexes. Potassium level is >10 mmol/L. The rhythm is unusually slow at <30 beats per minute with unusually wide QRS complexes with a left bundle branch block pattern, peaked T waves, and no P waves. This rhythm usually precedes asystole or ventricular fibrillation.


·   The normal serum potassium varies from 3.3 to 5.3 mmol/L. Hyperkalemia occurs when serum potassium exceeds 5.3 mmol/L. When extracellular potassium is increased, the ratio between intracellular and extracellular potassium is decreased and the resting membrane potential becomes less negative (<-90 mV). This will affect the height and velocity of phase 0 of the action potential. Slowing in conduction velocity in the atria and ventricles will cause widening of the P wave and QRS complex. As the severity of the hyperkalemia further increases, the resting potential becomes less and less negative resulting in further widening of the QRS complex and P wave. Hyperkalemia also shortens phase 2, which is equivalent to the plateau phase of the action potential. This will shorten the ST segment in the ECG resulting in a shorter QT interval. It also causes a more rapid phase 3 or steeper downslope of the action potential resulting in peaking of the T waves.

Figure 25.15: Marked Bradycardia with Wide Complexes, a Late Manifestation of Severe Hyperkalemia. The initial potassium level is unknown. After the patient was resuscitated, the potassium level was checked and found to be 8.8 mmol/L. The QRS complexes are wide with a very slow ventricular rate of 26 beats per minute. No P waves can be identified. Peaking of the T waves persists in V2 and V3.

·   Although the ECG findings may not consistently correlate with the level of serum potassium, the following are the ECG findings associated with increasing severity of hyperkalemia:

o    Mild hyperkalemia: <6.0 mmol/L

§  Increased amplitude with peaking of the T waves is the first abnormality to be detected when the potassium level rises between 5 and 6 mmol/L. Hyperkalemic T waves are typical and diagnostic in that the T waves are tall and pointed with a narrow base and a normal or short QT. The T waves become taller and more peaked as the level of hyperkalemia progresses. The diagnosis of hyperkalemia is untenable unless the above T-wave abnormalities are present. The T waves are often taller than the R waves in precordial leads V2 to V4.

§  The QT or corrected QT interval (QTc) is normal or shortened. It is prolonged only when hyperkalemia is associated with other electrolyte abnormalities such as hypocalcemia or when there is associated myocardial disease. This combination of hyperkalemia and hypo - calcemia is commonly seen in patients with chronic renal disease.

o    Moderate hyperkalemia: 6.0 to 7.0 mmol/L

§  Widening of the P wave and QRS complex starts to occur when the potassium level exceeds 6.0 mmol/L. Widening of the QRS complex may be mistaken for bundle branch block. Widening of the QRS complex associated with hyperkalemia is reversible after the electrolyte abnormality is corrected unlike preexistent bundle branch block, which is persistent.

§  Broadening of the P waves occurs when there is slowing of conduction of the impulse across the atria. When the P wave starts to widen, slight prolongation of the PR interval and varying degrees of AV block may occur.

o    Severe Hyperkalemia: >7.0 mmol/L

§  With increasing levels of serum potassium, further widening of the QRS complex occurs accompanied by shortening of the ST segment. The wide QRS complex will eventually merge into the tall and peaked T wave resembling a sine wave. The ST segments are often elevated in V1-2 and may be mistaken for acute ST elevation myocardial infarction.

§  Even when the rhythm remains normal sinus, the P wave may not be evident in the ECG. The absence of P waves in hyperkalemia even when the rhythm remains normal sinus is called sinoventricular rhythm. The absence of P waves may be due to slow conduction of the sinus impulse across the atria or the sinus impulse being conducted through special internodal tracts between the sinus node and AV node. Because the QRS complexes are no longer preceded by P waves, the rhythm is impossible to differentiate from AV junctional rhythm (when the QRS complexes are narrow) or accelerated idioventricular rhythm (when the QRS complexes are wide). Cardiac arrest may occur when the potassium level exceeds 8.5 mmol/L. This is preceded by marked slowing of the heart rate, further widening of the QRS complexes, asystole, or ventricular flutter/fibrillation.

Clinical Implications

·   Potassium is the major intracellular ion in the body. Approximately 98% of the total amount of potassium is intracellular and the remaining 2% extracellular. This difference in concentration between intracellular and extracellular potassium is due to the presence of sodium potassium adenosine triphosphatase pump where 3 units of sodium is pumped out of the cell in exchange for 2 units of potassium. The ratio between intracellular and extracellular potassium makes the resting membrane potential negative at approximately -90 mV.

·   Increased extracellular potassium may be due to increased potassium load, worsening renal function, or acute shift of intracellular potassium extracellularly. Increased potassium in the diet by itself rarely causes hyperkalemia. Some drugs can also cause hyperkalemia when there is renal dysfunction. These include potassium supplements, potassium sparing diuretics (triamterene and amiloride), aldosterone antagonists (spironolactone and eplerenone), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and non - steroidal anti-inflammatory agents including the selective cyclo-oxygenase 2 inhibitors. More commonly, hyperkalemia is due to renal failure. It may also be the result of acute shift of intracellular potassium to the extracellular space as when cells are damaged from hemolysis or rhabdomyolysis. Acidosis can also cause a shift of H+ ions into the cell in exchange for potassium that moves out of the cell. For every 0.1 unit decrease in blood pH, the level of potassium in the serum increases by approximately 0.5 mmol/L.

·   Among the electrolyte abnormalities, hyperkalemia causes the most remarkable ECG abnormalities. The ECG changes frequently parallel the severity of the electrolyte disorder. The expected ECG findings, however, may not correlate well with the potassium level because the effect of hyperkalemia on the ECG depends on several factors and not just the serum potassium level. These include the baseline level of potassium, the rate of rise of potassium in the blood, coexisting electrolyte abnormalities, coexisting metabolic abnormalities, and the presence or absence of myocardial disease.

·   Mild or moderate hyperkalemia is usually asymptomatic. When significant hyperkalemia occurs usually >7.0 mmol/L, symptoms include generalized weakness, paralysis, respiratory failure from respiratory muscle weakness, and cardiac arrest.

·   Among all the electrolyte abnormalities, hyperkalemia is the most fatal. Because severe hyperkalemia can be diagnosed in the ECG, this will allow emergency treatment of the electrolyte abnormality even before the results of the laboratory become available.

·   Similarly, the ECG is useful in the diagnosis of pseudohyperkalemia. The laboratory may mistakenly report a high potassium level not the result of actual hyperkalemia but from hemolysis after the blood is collected. If there are no associated ECG changes, the diagnosis of hyperkalemia is unlikely. This will obviate the need for unnecessary therapy.


·   Treatment should be tailored according to the severity of the hyperkalemia. The ECG abnormalities together with the serum potassium level serve as useful guide in dictating the intensity of management.

·   The American Heart Association (AHA) guidelines of cardiopulmonary resuscitation and emergency cardiovascular care recommend the following for the treatment of hyperkalemia.

·   Mild hyperkalemia, potassium level <6.0 mmol/L: Potassium level <6.0 mmol/L is seldom of great concern. The only therapy that may be needed is to identify the cause of the hyperkalemia so that further increases in serum potassium can be prevented. In addition, therapy may include removal of potassium from the body.

o    Loop diuretics: Furosemide 40 to 80 mg IV or bumetanide 1 mg IV to enhance excretion of potassium.

o    Cation-exchange resin: Sodium polystyrene sulfonate (Kayexalate) is given orally or by retention enema. The oral dose can vary from 15 to 60 g daily. Fifteen grams is given orally one to four times per day. Sorbitol 20%, 10 to 20 mL is given every 2 hours or as needed to prevent constipation. Lower doses of Kayexalate of 5 to 10 g may be given up to three times per day without laxative therapy. If the patient is unable to take the resin orally, it can be given as retention enema, 30 to 50 g every 6 hours in a warm emulsion such as 50 mL 70% sorbitol mixed with 100 to 150 mL tap water and retained for at least 30 to 60 minutes. Each gram of Kayexalate removes approximately 1 mmol of potassium and takes at least 30 minutes to 2 hours to take effect. The resin binder carries a high sodium load and should be given cautiously to patients in congestive heart failure. The resin can also bind other cations such as magnesium and calcium. These electrolytes should be monitored together with the level of serum potassium. Patients on digitalis should be monitored closely since hypokalemia can aggravate digitalis toxicity.

·   Moderate hyperkalemia, potassium level 6.0 to 7.0 mmol/L: When moderate hyperkalemia is present, therapy should be more emergent. In addition to eliminating the cause of the hyperkalemia and removal of excess potassium from the blood with loop diuretics and cation exchange resins, the level of serum potassium can be lowered more rapidly by shifting extracellular potassium intracellularly.

o    Glucose plus insulin: Twenty-five grams of glucose (50 mL 50% dextrose) is mixed with 10 units of regular insulin. The solution is injected IV for over 15 to 30 minutes. Ten units of regular insulin can also be mixed with 500 mL 10% glucose. The solution is given IV for 60 minutes. The effect may last for 4 to 6 hours.

Figure 25.16: The Electrocardiogram of Hypokalemia. (A-D) Varying levels of serum potassium. (A) Normal level of serum potassium. (B) Mild hypokalemia. A prominent U wave is present. (C) Moderate hypokalemia. The U wave becomes more prominent than the T wave. (D) Severe hypokalemia. There is fusion of the T and U waves.


o    Sodium bicarbonate: 50 mEq is given IV over 5 minutes. Sodium bicarbonate lowers extracellular potassium by shifting potassium into the cells. This agent is more effective when hyperkalemia is associated with metabolic acidosis. The effect may last for 2 hours and may be repeated as necessary.

o    Nebulized albuterol: 10 to 20 mg nebulized over 15 minutes. B2 agonists shifts extracellular potassium intracellularly and the effect may last for ≥2 hours. If insulin is being given concomitantly, albuterol can attenuate its hypoglycemic effect.

·   Severe hyperkalemia and critical hyperkalemia, potassium level >7.0 mmol/L: When serum potassium level exceeds 7.0 mmol/L or when the ECG abnormalities include absent P waves and changes in the QRS, ST segment and T waves, AV block or slowing of the heart rate, treatment of hyperkalemia should be very aggressive because severe hyperkalemia may cause lethal arrhythmias and cardiac arrest. The following agents are given in order of priority according to the AHA guidelines.

o    Calcium chloride: 10% 5 to 10 mL (500 to 1,000 mg) given IV over 2 to 5 minutes. Calcium does not lower the level of serum potassium but will stabilize myocardial membrane against the toxic effects of potassium, thereby lowering the risk of fatal arrhythmias including ventricular fibrillation. The effect of calcium is immediate but lasts only for 20 to 40 minutes and repeated dosing may be needed.

o    Sodium bicarbonate: 50 mEq given IV over 5 minutes. This should be injected using a separate tubing or IV line from that used for calcium chloride.

o    Glucose plus insulin: Mix 10 units of regular insulin with 50 mL 50% dextrose. The solution is given IV over 15 to 30 minutes.

o    Nebulized albuterol: 10 to 20 mg nebulized over 15 minutes.

o    Loop diuretics: as above.

o    Kayexalate enema: 15 to 60 g plus sorbitol given orally or rectally as above.

o    Dialysis: If above therapy is unsuccessful, emergent dialysis should be considered especially in patients with renal failure even if not previously on dialysis.


·   Severe hyperkalemia is the most fatal among all electrolyte abnormalities and is a medical emergency. Overall prognosis of hyperkalemia depends on the potassium level, efficacy of therapy, and comorbidities associated with the hyperkalemia. The presence of diabetic ketoacidosis and renal failure as the cause of the hyperkalemia often confer a poor prognosis.


·   Hypokalemia is defined as the presence of serum potassium that is lower than normal. The normal value for serum potassium is 3.3 to 5.3 mmol/L.

·   The most important ECG finding in hypokalemia is the presence of prominent U waves. As the hypokalemia becomes more profound, the amplitude of the T wave becomes lower as the size of the U wave becomes larger until both T and U waves bond together and become indistinguishable (Figs. 25.16 and 25.17).

·   Normal U wave: The U wave follows the T wave and is the last component of ventricular repolarization. The normal U wave is small measuring less than a quarter of the size of the T wave. The exact origin of the normal U wave is uncertain but is most probably from the repolarization of the Purkinje fibers.

·   Hypokalemic U wave: The U wave in hypokalemia is large and pathologic. It is much larger than the T wave and its origin is not the same as that of the normal U wave. It has been shown that in hypokalemia, the normal T wave becomes interrupted, splitting into two components. The T wave represents the first component and the U wave the second component. Thus, the Q-U interval truly represents the actual QT interval and is prolonged. The QT interval represents only the first component of the split T wave, and is equal to or even shorter than the normal QT interval (Figs. 25.18,25.19,25.20,25.21).

Figure 25.17: Prominent U Waves in Hypokalemia. Potassium level is 2.7 mm/L. The 12-lead electrocardiogram shows the classical finding of hypokalemia characterized by prominent U waves (arrows). Fusion of the T and U waves is seen in V3; thus, the T and U waves become indistinguishable.

Figure 25.18: The QT and the Q-U Interval in Hypokalemia. Lead V3 and lead II were simultaneously recorded. In lead II, the U waves are separately inscribed from the T waves and the two humps resemble the back of a camel. If the QT interval is measured in lead II, the QT interval is short since it represents only the first component of a split T wave. It does not represent the real QT interval. In V3, the U waves are very prominent and can not be separated from the T wave. This QU interval represents the actual QT interval and is prolonged. The 12-lead electrocardiogram is shown in Figure 25.17.

Figure 25.19: Prolonged QU Interval in Hypokalemia. Potassium level is 3.1 mmol/L. The U waves are prominent in V2-6 with prolonged QU interval.


Figure 25.20: Prominent U Waves and Prolonged QU Interval in Hypokalemia. Potassium level is 2.8 mmol/L. The U waves are more prominent than the T waves and are most prominent in V3 to V5. The QU interval is prolonged.

ECG Findings of Hypokalemia

·   Prominent U waves

·   Nonspecific ST depression and T-wave flattening as the U wave becomes more prominent

·   Prolongation of the QU interval

·   Fusion of the T and U waves

·   Ventricular arrhythmias, especially torsade de pointes


·   The ratio between intracellular and extracellular potassium determines the resting potential of a cell, which is normally -90 mV. When there is hypokalemia, extracellular potassium is decreased and the ratio between intracellular and extracellular potassium becomes higher. Thus, the cells become more negative than -90 mV and the resting potential is hyperpolarized. This will cause lengthening of the duration of the action potential resulting in a longer QT interval in the surface ECG. This will increase the frequency of ventricular arrhythmias especially torsade de pointes.

·   The ECG hallmark of hypokalemia is the presence of prominent U waves and prolongation of the QU interval. As hypokalemia worsens, the T wave flattens, a U wave emerges, and a seesaw effect between the amplitude of the T and U wave occurs. As the U wave grows larger, the T wave becomes smaller. Merging of the T and U waves eventually occur; thus, the T and U waves become indistinguishable from one another.

Figure 25.21: Hypokalemia with “Roller Coaster” ST-T Configuration. Potassium level is 1.7 mmol/L. The T waves have merged with the U waves in V4-6. The QU interval is prolonged with a “roller coaster” configuration in V2-6.

·   In hypokalemia, phase 3 of the transmembrane action potential is less steep causing a small or attenuated intramyocardial voltage gradient, resulting in low T waves. This is opposite to that of hyperkalemia, where phase 3 has a steeper slope, which translates into a higher intramyocardial voltage gradient, resulting in T waves that are taller and more peaked.

·   According to Yan et al., the mechanism of a pathologic U wave resulting from hypokalemia is different from the mechanism of a normal U wave. When hypokalemia is present, the abnormal T-U complex has been shown to be due to splitting of the ascending limb of the normal T wave into two components. The first component of the split T wave is the original T wave and the other component becomes a separate U wave, which is actually the other half of the split T wave. If only the QT interval is measured, which represents only the first component of the bifid T wave, the QT interval is equal to or even shorter than the normal QT interval. Thus, in hypokalemia, measurement of the true QT interval should include the U wave and is measured as the QU interval.

Clinical Implications

·   The normal level of potassium in the blood is 3.3 to 5.3 mmol/L. Hypokalemia refers to the presence of lower than normal potassium in the blood, which is <3.3 mmol/L.

·   The normal daily intake of potassium varies from 80 to 120 mEq/day. Almost 90% of dietary potassium is excreted by the kidneys and the rest by the gastrointestinal (GI) tract.

·   Hypokalemia usually occurs from potassium loss in the kidneys, frequently brought about by chronic diuretic therapy or potassium loss in the GI tract as a result of frequent vomiting, continuous gastric suction, or diarrhea.

·   Hypokalemia also occurs when there is acute shift of extracellular potassium intracellularly from metabolic alkalosis or drugs such as insulin and beta agonists. Alkalosis causes extracellular potassium to move into the cell in exchange for H+, resulting in a lower level of serum potassium. Metabolic alkalosis decreases serum potassium by 0.8 mmol/L for every 0.1 unit increase in pH above normal. Acidosis causes a reverse effect with intracellular potassium moving out of the cell in exchange for H+. Thus, an acidotic patient with a normal potassium level is expected to develop hypokalemia once the acidosis is corrected.

·   Symptoms of hypokalemia usually occur when significant electrolyte depletion has occurred. This is usually manifested as generalized weakness, fatigue, and paralysis. In patients who are being weaned off a respirator, it is important that potassium level should be checked because hypokalemia can cause muscle weakness that can result in respiratory failure. If hypokalemia is present, the electrolyte abnormality should be corrected. Hypokalemia can affect the muscles of the GI tract, resulting in ileus or constipation. It can also affect the muscles of the lower extremities, resulting in leg cramps and paresthesias.

·   Arrhythmias including torsade de pointes and pulseless electrical activity may occur when the QT (or QU) interval is prolonged.


·   Because potassium is predominantly an intracellular ion, hypokalemia may occur even when total body potassium is normal or higher than normal. Generally however, when hypokalemia is present and is from chronic loss of potassium, a decrease in serum potassium of 1 mmol/L is equivalent to a deficit of approximately 150 to 400 mmol of body potassium.

·   Therapy of hypokalemia includes identification and correction of the underlying abnormality.

·   Aggressive intravenous replacement of potassium may be associated with hyperkalemia and cardiac arrhythmias. Thus, intravenous administration of potassium is preferred when arrhythmias are present or when hypokalemia is severe (<2.5 mEq/L). Oral replacement is given if the patient is clinically stable without arrhythmias and the potassium level is ≥2.5 mmol/L because administration of potassium orally is much safer and can be given in higher doses.

·   Replacement therapy of approximately 200 to 300 mmol potassium is needed to increase the serum potassium level by 1 mmol/L. However, it may take several days to correct the electrolyte abnormality because the administered potassium is also excreted in the urine. Since intravenous replacement of potassium can potentially cause cardiac arrhythmias, the AHA guidelines recommend the following:

o    The maximum infusion of potassium should not exceed 10 to 20 mmol/hour and should be infused under continuous cardiac monitoring.

o    Potassium when given >20 mmol/hour should be infused with a central line. This concentration of potassium may be painful when given IV because it may cause sclerosis of the veins. The tip of the central catheter should not extend to the right atrium or ventricle because this may cause local hyperkalemia.

o    If severe life-threatening arrhythmias are present and a more rapid infusion is necessary, an initial infusion of 10 mmol IV is given over 5 minutes and repeated once if necessary.

·   Potassium is preferably mixed with non-glucose solutions to prevent insulin secretion, which can shift potassium intra - cellularly.

·   Hypokalemia is usually associated with other electrolyte abnormalities, especially hypomagnesemia. When there is hypomagnesemia, it might be difficult to correct the potassium deficiency because magnesium is necessary for the movement of electrolytes in and out of the cell including potassium; therefore, correcting both electrolyte abnormality should be done simultaneously.

·   The use of potassium sparing diuretics should be considered in hypokalemic patients requiring long term diuretic therapy.


·   Hypokalemia can cause ventricular arrhythmias and may be fatal if left uncorrected. It is usually from aggressive use of diuretics or gastrointestinal losses. Unlike patients with hyperkalemia, the renal function in hypokalemic patients is usually preserved. After the hypokalemia is corrected, prognosis will depend on the underlying cause of the hypokalemia.

Figure 25.22: The Electrocardiogram of Hypercalcemia. Diagrammatic representation of the electrocardiogram changes associated with hypercalcemia. (A) Normal. (B) Hypercalcemia: the ST segment is shortened because of shortening of phase 2 of the action potential.(C) Hypercalcemia with ST segment elevation. Fusion of the QRS complex and T wave occur due to further shortening of the ST segment.


·   Hypercalcemia refers to the presence of elevated calcium level above normal. The normal level of total serum calcium varies from 8.5 to 10.5 mg/dL or for ionized calcium 4.2 to 4.8 mg/dL.

·   When extracellular calcium is increased, the duration of the action potential is shortened. Shortening of the action potential duration results in shortening of the QT interval.

·   The ECG findings of hypercalcemia include (Figs. 25.22 and 25.23):

o    Shortening of the QT interval. This is due to shortening of phase 2 of the action potential corresponding to the ST segment in the ECG.

o    Elevation of the ST segment especially in the precordial leads. This may be mistaken for acute ischemic injury.

Figure 25.23: The ST and T Wave Configuration in Hypercalcemia. Total calcium level is 16.0 mg/dL. Note the short ST segment and ST elevation in V3 to V5. Prominent J wave or Osborn wave may also occur when there is hypercalcemia.

ECG Findings of Hypercalcemia

·   Short QT interval from shortening of the ST segment

·   Flattened and widened T wave with ST elevation

·   Prolonged P-R interval

·   Widened QRS complex

·   Increased QRS voltage

·   Notching of the terminal portion of the QRS complex from a prominent J wave

·   AV block progressing to complete heart block and cardiac arrest when serum calcium <15 to 20 mg/dL.


·   Increasing levels of serum calcium may cause changes in the ECG. Unlike hyperkalemia, in which the ECG changes are more dramatic, the ECG abnormalities associated with hypercalcemia are less specific and should not be used as the basis for making the diagnosis of hypercalcemia.

o    Hypercalcemia shortens the duration of the action potential of the myocyte, resulting in a shortened QT interval. This usually occurs when the serum calcium is >13 mg/dL. Because the duration of ventricular systole is shortened, ventricular refractoriness is shortened, rendering the patient more prone to arrhythmias. It also renders patients more susceptible to the toxic effects of digitalis.

o    Hypercalcemia initially increases inotropicity and chrono - tropy by causing increased calcium influx and decreases calcium egress in the myocyte. However, as serum calcium further increases to levels >15 to -20 mg/dL, myocardial contractility becomes depressed.

o    Very high levels of calcium, >15 to 20 mg/dL, may result in arrhythmias most commonly bradycardia and complete heart block.

Clinical Significance

·   Calcium is the most common mineral in the body; 99% of the total amount of calcium is stored in bones. The remaining 1% is distributed in the sera, 50% of which is bound to albumin and the rest available as ionized calcium. Total serum calcium is affected by the level of serum albumin. When serum albumin is low, total calcium is low. Inversely, when serum albumin is high, the total calcium level is high. The level of ionized calcium, however, is not affected by the level of serum albumin and is more important in causing signs and symptoms of calcium excess or deficiency.

·   Pseudohypercalcemia can occur when there is profound dehydration, causing increased binding of calcium by albumin. This will result in increased total serum calcium but the level of ionized calcium remains normal. This can also occur in some patients with multiple myeloma.

·   The normal level of total serum calcium is 8.5 to 10.5 mg/dL and of ionized calcium 4.2 to 4.8 mg/dL. Hypercalcemia indicates the presence of high levels of serum calcium above the normal range. When real hypercalcemia is suspected, the level of ionized calcium should be checked. Ionized calcium is collected anaerobically, adjusted to a normal pH of 7.4, and is often reported as normalized calcium.

·   The level of ionized calcium is actively regulated by the endocrine system. When there is hypocalcemia, enhanced secretion of parathyroid hormone (PTH) increases osteoclastic activity and bone resorption, thus increasing the level of calcium in the blood. PTH also promotes absorption of calcium in the GI tract by activating Vitamin D and decreases excretion of calcium in the kidneys by promoting tubular reabsorption. Inversely, when there is increased level of calcium, PTH secretion is inhibited and calcitonin is released, which will lower serum calcium by reducing osteoclastic activity and increasing the deposition of calcium in the bones and at the same time increase excretion of calcium by the kidneys.

·   Ionized calcium is affected by pH, whereas total calcium is not. When there is metabolic or respiratory alkalosis, H+ is shifted from plasma proteins to serum to buffer the increased bicarbonates. More ionized calcium will become proteinbound to neutralize the more negatively charged plasma protein, thus decreasing the level of ionized calcium. The reverse happens when there is acidosis: ionized calcium increases in the serum.

·   The two most common causes of hypercalcemia accounting for more than 90% of cases are hyperparathyroidism and malignancy.

o    Hyperparathyroidism may be primary from an autonomously hyperfunctioning parathyroid gland (primary hyperparathyroidism) or secondary from chronic renal disease (secondary hyperparathyroidism).

o    Hypercalcemia of malignancy is due to increased osteoclastic activity, resulting in increased bone resorption. This may be due to increased hormonelike substances in the blood or direct invasion of tumor cells into the bone.

§  Humoral hypercalcemia: from increase in PTH-like substances in the blood, resulting in increase osteoclastic activity and bone resorption. This type of hypercalcemia is seen in squamous cell cancer of the lungs, head and neck, and often renal and ovarian cancer.

§  Bone metastasis: direct bone metastasis may also result in increased bone resorption most commonly the result of breast cancer or multiple myeloma.

o    Other causes of hypercalcemia include use of drugs such as thiazide diuretics, lithium, and vitamins A and D or sarcoidosis and other granulomatous diseases.

·   There are usually no physical findings associated with the hypercalcemia itself. Symptoms of hypercalcemia usually do not occur until the serum calcium reaches 12 mg/dL or higher. Hypertension is common in patients with hypercalcemia and is a common manifestation in patients with primary hyperparathyroidism. At serum levels of 12 to 15 mg/dL, weakness, apathy, fatigue, depression, and confusion may occur. GI symptoms of constipation and dysphagia are common. A higher incidence of dyspepsia and peptic ulcer disease may occur because of a calcium-mediated increase in gastrin secretion. As hypercalcemia becomes more severe, dehydration may occur because hypercalcemia decreases renal concentrating capacity, resulting in polyuria and polydipsia. Finally, neurologic symptoms characterized by hallucinations, disorientation, and coma may develop. Although symptoms of hypercalcemia are usually neuromuscular, cardiac manifestations may occur, including AV block and cardiac arrest.


·   Treatment is directed toward the underlying cause of the hypercalcemia. Therapy for hypercalcemia is essential when the calcium level is >12 mg/dL, especially when the patient is symptomatic. Therapy is mandatory at levels >15 mg/dL, regardless of symptoms.

·   Excessive increase of calcium in the blood causes polyuria and GI symptoms, especially in patients with malignancy, resulting in dehydration. This enhances reabsorption of calcium in the kidneys, thus further worsening hypercalcemia. Patients with hypercalcemia are therefore volumecontracted; proper hydration with restoration of extracellular volume promotes calcium excretion.

o    Saline diuresis: In symptomatic patients with severe hypercalcemia >15 mg/dL who have reasonably preserved cardiovascular and renal function and are dehydrated, the 2005 AHA guidelines for cardiopulmonary resuscitation and emergency cardiovascular care recommends intravenous infusion of 300 to 500 mL/hour of 0.9% saline until any fluid deficit is corrected or until patient starts to diurese adequately. After the patient is properly hydrated, IV hydration is continued at 100 to 200 mL/hour to maintain adequate diuresis and promote calcium excretion. At least 3 to 4 L is usually needed in the first 24 hours. Other electrolytes, especially potassium and magnesium, should be monitored carefully.

o    Loop diuretics: Loop diuretics (e.g., furosemide [20-40 mg 2 to 4 times daily] or bumetanide [1 to 2 mg twice daily]), may be used in patients with heart failure, although their use in the treatment of the hypercalcemia itself is controversial and should be used only after appropriate volume repletion with normal saline. Thiazide diuretics should not be substituted for loop diuretics because they prevent calcium excretion.

·   Calcitonin: Calcitonin lowers serum calcium by inhibiting bone resorption and promoting urinary calcium excretion.

·   Bisphosphonates: Biphosphonic acid lowers serum calcium by inhibiting osteoclastic bone resorption. The following bisphosphonates are commonly used in the treatment of hypercalcemia associated with malignancy.

o    Pamidronate: Pamidronate is given as an intravenous infusion. It can be combined with calcitonin to provide a longer effect. There is risk of renal toxicity if given rapidly or in high doses.

o    Zoledronic acid: Zoledronic acid is preferred as it is more potent than pamidronate. It can be infused over a shorter period. The drug can also cause renal damage if the infusion is given rapidly or in high doses. Renal function should be reassessed if a second infusion is necessary. Patients receiving the infusion should be properly hydrated.

·   Steroids: Glucocorticoids reduce calcium level by several mechanisms. They inhibit intestinal absorption, increase urinary excretion of calcium, and have cytolytic effect to some tumor cells, especially multiple myeloma and other malignancies. They also inhibit calcitriol production by mononuclear cells in lungs and lymph nodes; thus, they are effective in hypercalcemia associated with granulomatous diseases and occasionally with lymphoma.

·   Phosphates: Phosphates are given orally to prevent calcium absorption. It combines with calcium to form complexes that limits its absorption. It also increases calcium deposition in bones.

·   Hemodialysis: Hemodialysis should be considered when there is need to promptly decrease the level of serum calcium in patients with heart failure or renal failure who cannot tolerate saline infusion. The dialysis fluid should be altered because the conventional dialysis solution may have a composition that may not be ideally suited for rapid correction of the electrolyte abnormality.


·   Prognosis depends on the underlying condition. Hypercalcemia is commonly associated with malignancy; thus, the intensity of therapy should be individualized and should consider the overall clinical picture.


·   Hypocalcemia is defined as a calcium level below the normal range. The normal serum calcium level varies from 8.5 to 10.5 mg/dL and the normal level of ionized calcium is 4.2 to 4.8 mg/dL.

·   When the level of extracellular calcium is decreased, the following ECG changes occur:

o    The QT interval is prolonged. Prolongation of the QT interval is due to prolongation of phase 2 of the action potential, which corresponds to the ST segment in the ECG. Thus, prolongation of the QT interval is mainly due to prolongation of the ST segment. The T wave is not significantly affected. Terminal inversion of the T waves may occur (Figs. 25.24,25.25,25.26,25.27).

o    Heart block may occur when the hypocalcemia is more severe.

Figure 25.24: The QT Interval of Hypocalcemia and Hypokalemia. In hypokalemia, the prolongation of the QT or QU interval is due to the presence of prominent U waves (B). In hypocalcemia, prolongation of the QT interval is primarily due to lengthening of the ST segment (C).


Figure 25.25: Prolonged ST Segment in Hypocalcemia. Total serum calcium is 7.6 mg/dL. The QT interval is prolonged from lengthening of the ST segment. The T waves are narrow as shown in V4 to V6.

Figure 25.26: ST Segment and T Wave Changes Associated with Hypocalcemia. Serum calcium is 7.2 mg/dL. The QT interval is prolonged with ST depression and narrow T waves.

Figure 25.27: Hypocalcemia and Hyperkalemia. Potassium level is 5.6 mmol/L and total calcium is 6.8 mg/dL. This electrolyte abnormality is commonly seen in renal failure. The T waves are peaked due to hyperkalemia and QTc is prolonged measuring 491 milliseconds from hypocalcemia.

ECG Abnormalities of Hypocalcemia

·   Prolonged QT interval due to lengthening of the ST segment.

·   Flat ST segment and terminal T-wave inversion.

·   Heart block and ventricular fibrillation when hypocalcemia is severe.


·   ECG findings include:

o    Prolongation of the QT interval. Prolongation of the QT interval is due to lengthening of phase 2 of the action potential. Because phase 2 of the action potential corresponds to the ST segment, prolongation of the QT interval is mainly from lengthening of the JT interval, which represents the interval between the end of the QRS complex and the end of the T wave. Although the ST segment lengthens, the size of the T wave is not altered. This is the most diagnostic ECG abnormality associated with hypocalcemia. This is in contrast to hypokalemia where a prominent U wave is present resulting in prolongation of the QT (QU) interval. Other ECG findings include flat ST segment, widening of the QRS complex, and AV block. Ventricular fibrillation may occur when hypocalcemia is severe.

Clinical Implications

·   Hypocalcemia refers to a low level of serum calcium below the normal range of 8.5 to 10.5 mg/dL (or 2.1 to 2.6 mmol/L). It is also defined as below the normal level of ionized calcium, which is 4.2 to 4.8 mg/dL (or <1.0 mmol/L).

·   The recommended daily calcium is 1,200 mg. Hypocalcemia can occur when there is:

o    Decreased intake or diminished absorption of calcium: Vitamin D is necessary for absorption of calcium in the GI tract. Vitamin D deficiency can occur in patients who are not exposed to sunlight or do not have adequate vitamin D in the diet. In chronic renal failure, there is defective hydroxylation of vitamin D to active vitamin D. Secondary increase in PTH may occur in an effort to maintain serum calcium levels.

o    Parathyroid hormone deficiency: This is usually the result of inadvertent removal of the parathyroid glands during thyroid surgery. The parathyroid glands are also affected by tumor or by infiltrative disorders, such as hemochromatosis or sarcoidosis.

o    Alkalosis: Metabolic or respiratory alkalosis decreases the level of ionized calcium.

o    Chelation of calcium with citrate and other substances: Hypocalcemia may occur following transfusion of >6 units of citrated blood. Increased phosphates from acute renal failure and exogenous bicarbonates and free fatty acids during acute pancreatitis can also result in chelation of calcium.

·   Signs and symptoms of hypocalcemia are dependent not only on the level of free or ionized calcium, but also on the rapidity in which calcium declines. In renal patients, hypocalcemia may not be clinically manifest because of coexistent acidosis, which increases the level of ionized calcium and may abruptly manifest only when the acidosis is corrected.

·   Symptoms of hypocalcemia usually do not occur until the level of ionized calcium falls below 0.7 mmol/L. This includes generalized irritability, hyperreflexia, muscle cramps, tetany, carpopedal spasm, seizures, and neuromuscular excitability characterized by a positive Chvostek and Trousseau signs.

o    Chvostek sign is elicited by tapping the facial nerve on the face anterior to the ear resulting in twitching of the facial muscles on the same side.

o    Trousseau sign involves inflating a blood pressure cuff above the systolic pressure for 3 minutes, resulting in muscular contraction with flexion of the wrist, thumbs, and metacarpophalangeal joints and hyperextension of the fingers.

·   Although symptoms of hypocalcemia are predominantly neuromuscular and include weakness, tetany, confusion and seizures, hypocalcemia can also cause arrhythmias, decrease in myocardial contractility, heart failure, and hypotension.

·   Hypocalcemia usually develops in association with other electrolyte abnormalities such as hyperkalemia and hypomagnesemia. The combination of hypocalcemia and hyperkalemia is commonly seen in patients with renal failure.


·   Treatment of hypocalcemia includes measurement of the ionized level of serum. When symptoms are present, calcium should be given intravenously even before the result of ionized calcium is available. Between 100 and 300 mg of elemental calcium is given intravenously, which will increase serum calcium for 1 to 2 hours; thus, repeated doses may be necessary. Calcium is given as calcium chloride or calcium gluconate. Calcium chloride has a higher amount of elemental calcium compared to calcium gluconate:

o    Calcium chloride 10% 10 mL contains 360 mg of elemental calcium, whereas calcium gluconate 10% 10 mL contains 93 mg of elemental calcium.

o    Calcium is given IV over 10 minutes (90 to 180 mg elemental calcium) followed by an IV drip of 540 to 720 mg in 500 to 1,000 mL D5W. The serum calcium level should be monitored every 4 to 6 hours and maintained at the low normal range of 7 to 9 mg/dL.

o    Calcium should be injected cautiously to patients receiving digitalis because it may cause digitalis toxicity.

·   If symptoms are not present, oral calcium supplements 1 to 4 g daily in divided doses may suffice.

·   Therapy includes correction of other electrolyte abnormalities because calcium entry into the cells is dependent on the presence of normal levels of magnesium and potassium.


·   Prognosis of patients with hypocalcemia will depend on the underlying medical condition.

Suggested Readings

2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Part 10.1: life-threatening electrolyte abnormalities. Circulation.2005;112:IV-121-I-125.

Agus ZS. Etiology of hypercalcemia. 2008 UpToDate. www.utdol. com.

Agus ZS, Berenson JR. Treatment of hypercalcemia. 2008 UpToDate.

Dagogo-Jack S. Mineral and metabolic bone disease. In: Carey CF, Lee HH, Woeltje KF, eds. The Washington Manual of Medical Therapeutics. 29th ed. Philadelphia: Lippincott Williams & Wilkins; 1998:441-455.

Gibbs MA, Wolfson AB, Tayal WS. Electrolyte disturbances. In: Marx JA, ed. Rosen's Emergency Medicine, Concepts and Clinical Practice. 5th ed. St. Louis: Mosby; 2002:1724-1744.

Inzucchi SE. Understanding hypercalcemia. Postgrad Med. 2004; 115:69-76.

Palmer BF. Managing hyperkalemia caused by inhibitors or the renin-angiotensin-aldosterone system. N Engl J Med. 2004; 351:585-592.

Rose BD. Clinical manifestations and treatment of hyperkalemia. 2008 UpToDate.

Rose BD. Clinical manifestations and treatment of hypokalemia. 2008 UpToDate.

Rutecki GW, Whittier FC. Recognizing hypercalcemia: the “3-hormone, 3-organ rule.” J Crit Illness. 1998;13:59-66.

Singer GG. Fluid and electrolyte management. In: Carey CF, Lee HH, Woeltje KF, eds. The Washington Manual of Medical Therapeutics. 29th ed. Philadelphia: Lippincott Williams & Wilkins; 1998:39-60.

Urbano FL. Signs of hypocalcemia: Chvostek's and Trousseau's signs. Hosp Physician. 2000;36:43-45.

Yan GX, Shimizu W, Antzelevitch C. Cellular basis for the normal T-wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation. 1998;98:1921-1927.

Yan GX, Lankipalli RS, Burke JF, et al. Ventricular repolarization components of the electrocardiogram, cellular basis and clinical significance. J Am Coll Cardiol. 2003;42: 401-409.

Zaloga GP, RR Kirby, WC Bernards, et al. Fluids and electrolytes. In: Civetta JM, Taylor RW Kirby RR, eds. Critical Care. 3rd ed. Philadelphia: Lippincott-Raven Publishers; 1997:413-429.