Course Authors

Martin J. Carey, M.D.

Dr. Carey reports no conflict of interest.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 0.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 

Learning Objectives

Upon completion of this Cyberounds^®, you should be able to:

 

It is 01:00 and you are the only physician in a small ER. You have just discharged one patient, but before you can sit down with your first cup of coffee of the shift, the ambulance arrives with a 75-year-old male, from one of the local nursing homes. The emergency medicine technician gives you the history as related to her in the nursing home. The patient was apparently a little "unwell" all day. He had gone to bed early, but when he was checked at midnight he "did not seem to be responding well." Apparently, he had "something wrong with his heart and with his kidneys," and mild Alzheimer's disease. He was on no medications. He had been in the nursing home for just five days, while his wife, daughter and son-in-law, with whom he usually lived, were visiting a sibling in Australia for two weeks. There was no letter from the nursing home, and the patient's name did not come up on the hospital computer system.

The patient was taken into a monitored bed space. While being hooked up to the BP machine and the monitor, you notice that he opens his eyes to voice, will weakly move all limbs, but not obey commands, and is mumbling incoherently. A pulse is weak and thready at the wrist, with a rate of about 80 and regular. The BP machine springs to life and tells you he has a BP of 80/52. His respiration rate is steady at 22. An O2 saturation is recorded at 91%. The nurse places nasal cannullae and turns the oxygen to 4 Liters/minute. His oxygen saturation increases to about 94%. On the EKG monitor, this is what you see:

Figure 1. Initial Rhythm Strip.

1. What is the diagnosis and what is the usual immediate treatment? Under what circumstances would this NOT be the correct therapeutic option?
2. What exactly will you do after the initial treatment?
3. Why do these treatment options work?
4. What are some of the causes of this problem?

Answers and Discussion

What Is the Diagnosis, and What Is the Usual Immediate Treatment? Under What Circumstances Would This NOT Be the Correct Therapeutic Option?

The diagnosis is HYPERKALEMIA. Hyperkalemia is defined as a serum potassium of greater than 5.2 mEq/L. This patient had a serum potassium of 10.2mEq/L, a blood urea nitrogen of 202mg/dL and a serum creatinine of 21mg/dL. The presence of severe hyperkalemia, especially with EKG changes, is a life-threatening emergency. The EKG shows the classic picture of peaked T waves, widened QRS complex and absent P waves. (Initially the PR interval may lengthen, but gradually the P wave disappears) Eventually the EKG may resemble a sine wave. The patient may then degenerate into ventricular fibrillation, or sometimes asystole. Heart block, and virtually any other cardiac arrhythmia may also occur. Note that the effects of hyperkalemia are worse in the presence of hyponatremia, acidosis, or hypocalcemia. Unfortunately, the EKG changes do not always progress in an organized way. Patients who have minimal changes one minute may be in ventricular fibrillation the next. In addition to the EKG changes the patient may describe abdominal pain, diarrhea and muscle pain or weakness. The physical examination, though, is often normal.(7),(8)

As with all acute situations, the initial therapy should be directed towards control of the airway, ensuring adequate ventilation, and supporting the circulation. Once these immediate factors are under control, the specific issue of management of the hyperkalemia is addressed. The immediate treatment for severe hyperkalemia with EKG changes is intravenous calcium. Calcium is available as either 10% calcium gluconate, which contains 4.6mEq/L, or 10% calcium chloride, which contains 13.6mEq/L. The dose of the gluconate form is 10-20 mls; the dose of the chloride is 5-10 mls. The effect of calcium on the EKG is seen within two to three minutes. The patient received 10 mls of calcium chloride. Some authors favor the use of two to four ampules of 10mls of 10% calcium gluconate, as this form of calicium releases ionized calicium into the circulation more slowly and is less likely to cause skin necrosis if extravasated.(4) Three minutes later the patient's EKG was:

Figure 2. EKG after 10 mls of Calcium.

There have been case reports of survival after cardiac arrest due to hyperkalemia, even after prolonged resuscitation.(1) In these cases, the theory is that many patients who experience arrest due to hyperkalemia do not have primary end stage cardiac disease. Always consider the diagnosis in renal patients, or indeed any patient with the risk factors mentioned below, who arrests.

Calcium is used with great caution, if at all, if the hyperkalemia is related to digoxin toxicity. In this situation the immediate use of a digoxin binding antibody is indicated. Calcium will exacerbate digoxin toxicity.(6)

What Exactly Will You Do After the Initial Treatment?

Once the acute situation is under control - the beneficial effects of the calcium will last about one hour - it is time for additional treatment. Note that if the first dose of calcium is not effective it can be repeated after five minutes. A calcium infusion, at 5-10 mEq/hour, may also be used if necessary. Sometimes calcium alone is not effective, and it is necessary to rapidly introduce the following measures.(7),(8)

In the emergency department the next step is usually the administration of sodium bicarbonate. A 50 mEq bolus (50 mls of 8.4% sodium bicarbonate) is administered over five to 10 minutes. The onset of action is within 10 minutes, and the effects last two hours or so. The dose can be repeated in 15 minutes if needed. Bicarbonate is particularly useful in the setting of severe inorganic metabolic acidosis, in which the potassium level may increase between 0.5 and 1.2mEq/L for each 0.1 unit change in pH. In respiratory acidosis and organic (e.g. lactate) metabolic acidosis the potassium level may only increase by 0.1 to 0.3 mEq/L for every 0.1 unit change in pH. Administration of bicarbonate may cause volume overload, and can also precipitate tetany if the patient is hypocalcemic, because of the decrease in the serum ionized calcium level which occurs with alkalosis.

Insulin and glucose are the next step. The glucose is administered to prevent hypoglycemia. The dose schedules for the administration of glucose and insulin vary by institution. In this instance, the patient received a bolus of 10 units of regular insulin, together with 50 grams of glucose infused over one hour. The ratio of 1 unit insulin to 5 grams of glucose is usual, though some authors believe that the ratio should be 1 unit to 10 grams. Hyperglycemia should be avoided, though, as it can exacerbate the hyperkalemia by increasing plasma tonicity, and thus exerting an osmotic drag effect. Note that insulin alone is effective if the patient is hyperglycemic, though in this situation the patient may actually have a total body potassium deficit, and can rapidly become hypokalemic as the potassium is returned to the cells. Careful monitoring is required. The onset of action of insulin is about 30 to 60 minutes, and the effects last for about four to six hours. The infusion can be repeated as needed.

Agonists, such as albuterol, have been shown to decrease the serum potassium level by up to 1 to 1.5 mEq/L within 30 minutes of their administration. The usual dose is 10mgs by nebulizer. The effects are seen within 10 minutes, and last for up to six hours.

In the acute situation, where the above measures are being instituted, but there has been little clinical response, the use of external cardiac pacing may be required in the setting of bradycardia, asystole or atrioventricular block.

Note that all of the above modalities have a relatively short effect, measured in hours rather than days. However, in the emergency departmentthey will usually work to correct the immediate life threatening cardiotoxicity. During this time efforts can be made to institute definitive therapy aimed at reducing the body load of potassium. This may be achieved through the use of a cation exchange resin such as 50 grams of sodium polystyrene sulfonate (Kayexalateref). This is usually administered rectally, though it can be given orally. It should be used with sorbitol to reduce the risk of constipation. Each gram of resin releases 2 mEq of sodium in exchange for 1 mEq of potassium. Colonic necrosis has been described following the use of rectal exchange resins with sorbitol.(2) The patients developing this complication are usually uremic, or post-renal transplantation. Rectal administration should be used with great care in these patients. Other adverse effects of the use of cation exchange resins are related to the absorption of large quantities of sodium, and thus fluid retention, which my precipitate cardiac failure or hypertension.

In patients with preserved renal function, potassium-losing diuretics, such as furosemide 40 mgs, can be used. They are particularly useful if there is fluid overload.

The most effective method for removal of potassium is through hemodialysis. If used with a potassium free dialysate up to 40mEq of potassium can be removed in the first hour. This rate of loss can be maintained throughout hemodialysis. The problem with this therapy is the time taken to prepare the equipment, and the vascular access needed. If hemodialysis is not available, peritoneal dialysis can be considered, though it is not nearly as efficient at removing potassium as hemodialysis.

Why Do These Treatment Options Work?

The aim of therapy is initially to oppose the effects of the hyperkalemia at the level of the cell membrane, then to reduce its plasma concentration, which is initially achieved by forcing potassium into cells, and finally to reduce the total body load of potassium by encouraging its excretion, or arranging its removal.

Membrane stabilization is achieved through the use of calcium, or, in the hyponatremic patient, the use of hypertonic saline. Recently, even in the hyponatremic patient, the use of hypertonic saline has mostly been superseded by the use of sodium bicarbonate. Hyperkalemia reduces the magnitude of the resting potential. Calcium lowers the threshold potential, thus normalizing the membrane excitability.

The plasma concentration is lowered by forcing the potassium into cells using glucose and insulin, sodium bicarbonate or adrenergic agonists. Sodium bicarbonate acts to move the potassium from the extracellular to the intracellular space. It achieves this through the increase in the serum pH, and through the rise in serum bicarbonate level. However, the effect can occur even without a change in measured serum bicarbonate levels, provided there is an increase in the pH. Insulin stimulates sodium/potassium adenosine triphosphate activity, and this action is independent of the transportation of glucose. The agonists work in a similar fashion. This increases the carriage of potassium into the cell.

The total body load of potassium is lowered using cation exchange resins, diuretics or either hemodialysis or peritoneal dialysis, as noted above.

What Are Some of the Causes of This Problem?

Some of the main causes of hyperkalemia are listed in the Table below. (This list is adapted from the paper by Latta et al.)(3)

Conclusion

The patient underwent each of the inteventions listed above. He was rehydrated, received two ampules of 50 mls of 8.4% bicarabonate, an insulin and dextrose infusion and oral ion exchange resins. He gradually regained consciousness. By the time he left the department on his way to dialysis, he was his usual garrulous self. His potassium had fallen to 7.2. A good job done. Perhaps now it was time for that cup of coffee.