A client is receiving furosemide. for which sign of hypokalemia will the nurse monitor the client?

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Hypokalemia is when blood’s potassium levels are too low. Potassium is an important electrolyte for nerve and muscle cell functioning, especially for muscle cells in the heart. Your kidneys control your body’s potassium levels, allowing for excess potassium to leave the body through urine or sweat.

Hypokalemia is also called:

• hypokalemic syndrome
• low potassium syndrome
• hypopotassemia syndrome

Mild hypokalemia doesn’t cause symptoms. In some cases, low potassium levels can lead to arrhythmia, or abnormal heart rhythms, as well as severe muscle weakness. But these symptoms typically reverse after treatment. Learn what it means to have hypokalemia and how to treat this condition.

Mild hypokalemia usually shows no signs or symptoms. In fact, symptoms generally don’t appear until your potassium levels are extremely low. A normal level of potassium is 3.6–5.2 millimoles per liter (mmol/L).

Being aware of hypokalemia symptoms can help. Call your doctor if you are experiencing these symptoms:

• weakness
• fatigue
• constipation
• muscle cramping
• palpitations

Levels below 3.6 are considered low, and anything below 2.5 mmol/L is life-threateningly low, according to the Mayo Clinic. At these levels, there may be signs and symptoms of:

• paralysis
• respiratory failure
• breakdown of muscle tissue
• ileus (lazy bowels)

In more severe cases, abnormal rhythms may occur. This is most common in people who take digitalis medications (digoxin) or have irregular heart rhythm conditions such as:

• fibrillation, atrial or ventricular
• tachycardia (heartbeat too fast)
• bradycardia (heartbeat too slow)
• premature heartbeats

Other symptoms include loss of appetite, nausea, and vomiting.

You can lose too much potassium through urine, sweat, or bowel movements. Inadequate potassium intake and low magnesium levels can result in hypokalemia. Most of the time hypokalemia is a symptom or side effect of other conditions and medications.

These include:

• Bartter syndrome, a rare genetic kidney disorder that causes salt and potassium imbalance
• Gitelman syndrome, a rare genetic kidney disorder that causes an imbalance of ions in the body
• Liddle syndrome, a rare disorder that causes an increase in blood pressure and hypokalemia
• Cushing syndrome, a rare condition due to long-term exposure to cortisol
• eating substances like bentonite (clay) or glycyrrhizin (in natural licorice and chewing tobacco)
• potassium-wasting diuretics, such as Thiazides, loop, and osmotic diuretics
• long-term use of laxatives
• high doses of penicillin
• diabetic ketoacidosis
• dilution due to IV fluid administration
• magnesium deficiency
• adrenal gland issues
• malnutrition
• poor absorption
• hyperthyroidism
• delerium tremens
• renal tubular acidosis types I and 2
• catecholamine surge, such as with a heart attack
• drugs such as insulin and beta 2 agonists used for COPD and asthma
• barium poisoning
• familial hypokalemia

Your risks for hypokalemia can increase if you:

• take medications, especially diuretics known to cause potassium loss
• have prolonged illness that causes vomiting or diarrhea
• have a medical condition like the ones listed above

People with heart conditions also have a higher risk for complications. Even mild hypokalemia can lead to abnormal heart rhythms. It’s important to maintain a potassium level of around 4 mmol/L if you have medical condition such as congestive heart failure, arrhythmias, or history of heart attacks.

Your doctor will usually discover if you’re at risk for or have hypokalemia during routine blood and urine tests. These tests check for mineral and vitamin levels in the blood, including potassium levels.

Read more about taking a potassium test »

Your doctor will also order an ECG test to check your heartbeat since hypokalemia and heart abnormalities are commonly linked.

Someone who has hypokalemia and shows symptoms will need hospitalization. They will also require heart monitoring to make sure their heart rhythm is normal.

Treating low potassium levels in the hospital requires a multi-step approach:

1. Remove causes:After identifying the underlying cause, your doctor will prescribe the appropriate treatment. For example, your doctor may prescribe medications to reduce diarrhea or vomiting or change your medication.

2. Restore potassium levels: You can take potassium supplements to restore low potassium levels. But fixing potassium levels too quickly can cause unwanted side effects like abnormal heart rhythms. In cases of dangerously low potassium levels, you may need an IV drip for controlled potassium intake.

3. Monitor levels during hospital stay: At the hospital, a doctor or nurse will check your levels to make sure the potassium levels don’t reverse and cause hyperkalemia instead. High potassium levels can also cause serious complications.

After you leave the hospital, your doctor may recommend a potassium-rich diet. If you need to take potassium supplements, take them with lots of fluids and with, or after, your meals. You may also need to take magnesium supplements as magnesium loss can occur with potassium loss.

Hypokalemia is treatable. Treatment usually involves treating the underlying condition. Most people learn to control their potassium levels through diet or supplements.

Make an appointment with the doctor if you’re showing symptoms of hypokalemia. Early treatment and diagnosis can help prevent the condition from developing into paralysis, respiratory failure, or heart complications.

About 20 percent of people in hospitals will experience hypokalemia, while only 1 percent of adults not in the hospital have hypokalemia. A doctor or nurse will usually monitor you during your stay to prevent hypokalemia from occurring.

Seek medical attention if you are experiencing vomiting or diarrhea for more than 24–48 hours. Preventing prolonged bouts of illness and loss of fluids is important to keeping hypokalemia from occurring.

Potassium-rich diet

Eating a diet that is rich in potassium can help prevent and treat low blood potassium. Discuss your diet with your doctor. You’ll want to avoid taking too much potassium, especially if you’re taking potassium supplements. Good sources of potassium include:

• avocados
• bananas
• figs
• kiwi
• oranges
• spinach
• tomatoes
• milk
• peas and beans
• peanut butter
• bran

While a diet low in potassium is rarely the cause of hypokalemia, potassium is important for healthy body functions. Unless your doctor tells you otherwise, eating a diet rich in potassium-containing foods is a healthy choice.

What happens when you have too much potassium? »

Furosemide is a loop diuretic that has been in use for decades. The Food and Drug Administration (FDA) has approved furosemide to treat conditions with volume overload and edema secondary to congestive heart failure exacerbation, liver failure, or renal failure, including the nephrotic syndrome. However, clinicians must be aware of updates related to the indications and administration of furosemide to ensure safe practices and minimize adverse effects. This activity reviews updates on the recommended use of furosemide, the mechanism of action, indications, contraindications, adverse effects, toxicity, and other key factors (e.g., off-label uses, dosing, pharmacokinetics, monitoring, relevant interactions) profile. It highlights the interprofessional team's role in caring for patients on furosemide therapy.

Objectives:

• Identify the mechanism of action of furosemide.

• Describe the contraindications to the use of furosemide.

• Outline the monitoring necessary for patients on furosemide.

• Explain how healthy collaboration and communication between interprofessional team members can optimize the use of furosemide and minimize adverse effects, thereby improving patient outcomes.

Access free multiple choice questions on this topic.

The Food and Drug Administration (FDA) has approved furosemide to treat conditions with volume overload and edema secondary to congestive heart failure exacerbation, liver failure, or renal failure, including the nephrotic syndrome.  

For patients with acutely decompensated heart failure (ADHF) with volume overload who have not received diuretics previously, the initial dose of furosemide should be 20 to 40 mg intravenously. Later, titrate the furosemide dose according to the clinical response of the patients. However, for those patients with ADHF with a normal kidney function on chronic diuretic therapy, the initial dose of furosemide can be equivalent to or greater than the total oral maintenance dose of furosemide the patient takes daily. Subsequently, the diuretic dose adjustments are according to the patient's clinical response. Nevertheless, starting with higher doses of furosemide, at a dose of 2.5 times the total daily oral dose of furosemide per day, has shown a significant trend toward a rapid improvement in the global assessment of patient symptoms.[1]

Although the FDA approved the use of loop diuretics alone or in combination with other anti-hypertensive medications as an alternative to thiazide diuretics to treat hypertension, however, the clinical guidelines panel report of the Eighth Joint National Committee (JNC-8) published in 2014 and the American College of Cardiology/American Heart Association (ACC/AHA) Task Force Panel Guidelines on hypertension treatment published in 2017 do not recommend the use of loop diuretic as a first-line medication to treat hypertension.[2][3] Nevertheless, Furosemide can be a second-line agent in heart failure patients with symptoms and advanced kidney disease with an estimated glomerular filtration rate of less than 30 ml per minute; loop diuretics (furosemide) are preferred over thiazide diuretics to treat hypertension.[4] 

Diuretic therapy is recommended in patients with liver cirrhosis and ascites, accompanied by dietary sodium restriction. The recommended diuretics are a combination of spironolactone and furosemide, starting at a ratio of 100 mg of spironolactone and 40 mg of furosemide. They are titrated up to the dose of diuretics in an increment of the same ratio until achieving an adequate response to diuretic therapy or reaching a maximum dose of 400 mg of spironolactone plus 160 mg of furosemide.[5] However, in cases of intolerance to diuretics secondary to borderline blood pressure, the diuretics can be started at relatively lower doses of 50 mg of spironolactone with 20 mg of furosemide.

Furosemide inhibits tubular reabsorption of sodium and chloride in the proximal and distal tubules and the thick ascending loop of Henle by inhibiting the sodium-chloride cotransport system resulting in excessive excretion of water along with sodium, chloride, magnesium, and calcium.[6]

Pharmacokinetics

Absorption: The onset of action of furosemide is usually within the first hour of oral furosemide intake, and it takes the first 1 to 2 hours to achieve a peak effect. The mean bioavailability of oral furosemide is 51% compared with the bioavailability of intravenously administered furosemide.[7]

Bioavailability:  The furosemide absorption is slower than normal in patients with edema, particularly in patients with decompensated heart failure; however, the amount of loop diuretic absorbed is normal.[8] Oral and sublingual administration of furosemide achieves a peak concentration slower than the iv route. Although furosemide is more avidly absorbed with a bioavailability of 59% via the sublingual route compared with the oral route of administration, i.e., 47%,  the half-life and time to peak concentration were not different between the oral and sublingual route of drug delivery. Also, the urinary excretion rate of furosemide and sodium and cumulative urine excretion rate was not different between the oral and sublingual administration of furosemide.[9].The bioavailability of furosemide is variable and relatively lesser than that of torsemide in patients with compensated congestive heart failure.[10][11] 

Distribution: In healthy individuals, greater than 95% of furosemide is bound to plasma protein, mainly albumin. Only 2.3% to 4.1% of furosemide is existent in an unbound form in therapeutic concentrations. 

Metabolism: Furosemide glucuronide is a major biotransformation active product of furosemide, having an active diuretic effect. Contemporary evidence indicates that furosemide is minimally metabolized in the liver.[12]

Excretion: The terminal half-life of furosemide is approximately 2 hours, and the total time of therapeutic effect is 6 to 8 hours. However, the half-life of furosemide will prolong in patients with chronic renal disease.[7] Although more furosemide gets excreted in the urine after IV administration, there is no difference in the amount of unchanged furosemide excretion in urine between the two formulations. After intravenous administration, furosemide achieves an early and high serum peak concentration and a higher peak excretion rate. A greater extent of furosemide is excreted in urine following the parenteral administration than oral administration.

Furosemide is available in oral and intravenous formulations. The administration of oral furosemide can be in the form of tablets or an oral solution. Intravenous furosemide is twice as potent as oral furosemide.

In patients with normal renal function, the oral dose equivalence of furosemide relative to other oral diuretics is as follows[13]:

• 40 mg of furosemide = 20 mg of torsemide = 1 mg of bumetanide

• Furosemide oral tablet formulations are available in 20 mg, 40 mg, and 80 mg.

• Furosemide oral solution is available as 10 mg/ml or 8 mg/ml, i.e., 40 mg furosemide/5 ml of solution.

Breaking phenomenon and ceiling effect: Normally, when an individual receives furosemide either orally or intravenously, it increases sodium excretion in urine. In a patient with extracellular volume expansion who has never had exposure to furosemide, the first dose of the drug causes significant sodium excretion and diuresis within the first 3 to 6 hours. After that effect of furosemide weans off, the kidney starts retaining sodium and chloride; this is called "post-diuretic sodium retention." Therefore, it is imperative to repeat the furosemide dose at 6 to 8-hour intervals to avoid post diuretic sodium retention and achieve significant diuresis. When furosemide is prescribed chronically, the patient's weight loss correlates with urine volume. A discrepancy in weight loss and diuresis indicates excessive sodium intake by the patient, which can be detected by 24-hour urine sodium collection.

In a normal person and patient with extracellular fluid (ECF) expansion, there is a linear relationship between ECF expansion and natriuresis when receiving furosemide; this means that the patient will have higher natriuresis and urine output if ECF volume expands as compared to a person with normal ECF volume. As furosemide use becomes chronic in a patient, ECF volume shrinks, and the level of natriuresis also goes down. At that point, the amount of natriuresis equals sodium intake; this is called the "breaking phenomenon." This phenomenon is adaptive when it occurs at low ECF volume. But in chronic heart failure patients with persistent ECF volume expansion, this phenomenon is maladaptive. Natriuresis is lower even when ECF volume becomes expanded. The reason for these maladaptive changes is remodeling in the distal nephron. There are hypertrophy and hyperplasia of distal segments of the nephron. These results from increased salt delivery, increased aldosterone, angiotensin II, and a change in potassium concentration; as a result of distal segment hypertrophy, sodium transport capacity increases which rivals furosemide's sodium absorption inhibiting capacity at the level of the thick ascending loop of henley. Clinicians can overcome this phenomenon by adding thiazide diuretics which block sodium absorption in distal segments of the nephron.[14][15]

Use in Specific Population

Patients with Hepatic Impairment: In patients with hepatic cirrhosis and ascites, furosemide therapy should be initiated in the hospital. In hepatic coma and states of electrolyte depletion, therapy should not be started until the underlying condition is improved. Sudden fluid and electrolyte balance alterations in patients with cirrhosis may precipitate hepatic encephalopathy; therefore, stringent observation is necessary during diuresis.

Patients with Renal Impairment: GFR ≤30 mL/min; increased doses are required to achieve desired diuretic response. If increasing azotemia and oliguria occur during severe progressive renal disease treatment, furosemide should be discontinued.

Pregnancy Considerations: Furosemide was a pregnancy category C drug under the old FDA categories, and clinicians should use caution in pregnant women after discussion with the patient about risks and benefits.[16] Furosemide is known to cross the placenta, and animal reproduction studies have shown adverse events. Although pregnant women with heart failure have had treatment with furosemide, a risk and benefits discussion should occur with the pregnant patient, and caution is necessary with the decision to take furosemide during pregnancy; fetal growth will require close monitoring.[17][18]

Breastfeeding Considerations: Because little information is available on using furosemide during breastfeeding and because intense diuresis might decrease lactation, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Low doses of furosemide may not suppress lactation.[19]

Adverse reactions are categorized below by the system organ classification system(soc) and listed by decreasing severity. The following are potential adverse effects associated with furosemide use[10][20]:

Gastrointestinal System

• Hepatic encephalopathy in patients with cirrhosis[21]

• Pancreatitis

• Jaundice (intrahepatic cholestatic jaundice)

• Increased liver enzymes

• Anorexia

• Oral and gastric irritation

• Cramping

• Diarrhea

• Constipation

• Nausea

• Vomiting

Systemic Hypersensitivity Reactions

• Severe anaphylactic or anaphylactoid reactions (e.g., with shock)

• Systemic vasculitis

• Interstitial nephritis

• Necrotizing angiitis

Central Nervous System:

• Paresthesias

• Vertigo

• Dizziness

• Headache

• Blurred vision

• Xanthopsia

Hematologic Reactions

• Aplastic anemia 

• Thrombocytopenia

• Agranulocytosis

• Hemolytic anemia

• Leukopenia

• Anemia

• Eosinophilia

Dermatologic-hypersensitivity Reactions

• Toxic epidermal necrolysis

• Stevens-johnson syndrome

• Erythema multiforme

• Drug rash with eosinophilia and systemic symptoms

• Acute generalized exanthematous pustulosis

• Exfoliative dermatitis

• Bullous pemphigoid

• Purpura

• Photosensitivity

• Rash

• Pruritus

• Urticaria

Cardiovascular System

• Alcohol, barbiturates, or narcotics may aggravate orthostatic hypotension.

• Increase in cholesterol and triglyceride serum levels

Renal Disorders

• Acute kidney injury due to fluid loss[23]

Metabolic Disorders

• Hyperglycemia

• Hyperuricemia

• Hypokalemia

Contraindications

• Contraindications to furosemide use include patients with documented allergies to furosemide and patients with anuria.

• A boxed warning suggests the cautious use of furosemide as it is a potent diuretic, which can predispose to excessive loss of water and electrolytes, resulting in dehydration with electrolyte depletion.

• According to Beers Criteria, caution is necessary when administering diuretics to patients 65 years and older to avoid potential adverse effects of inducing hyponatremia by causing or exacerbating syndrome of inappropriate antidiuretic hormone secretion (SIADH); therefore, close monitoring of serum sodium is advisable at initiation or during the dose adjustment in older adults.[25]

• Ototoxicity can occur with the use of furosemide, but the following conditions predispose patients to a higher risk of reversible or irreversible hearing impairment[26]:

  • Use of a higher than the recommended dose of furosemide or a fast infusion rate of the drug,

  • Hypoalbuminemia comorbid illnesses

  • The concomitant use of ethacrynic acid, aminoglycosides, or other ototoxic drugs

  • Patients with underlying severe renal impairment

• Caution is also necessary for patients with underlying liver disease, especially those with decompensated liver disease, as rapid electrolytes imbalance secondary to furosemide use can precipitate hepatic encephalopathy and hepatic coma. In patients with hepatic coma, the prescriber should delay giving furosemide until there is an improvement in the patient's mental status.[5]

• Patients with the advanced renal disease with fluid overload should be closely monitored for oliguria, azotemia, and volume status. If either oliguria or azotemia develops, furosemide should be discontinued to prevent kidney injury.

• In patients with primary adrenal insufficiency with hypertension, diuretics are a practice clinicians should avoid to treat hypertension. Alternatively, the dosage of glucocorticoid/mineralocorticoid requires adjustment, and, if needed, the Clinician should prefer other classes of antihypertensive agents over diuretics to treat hypertension.[27]

• High-risk patients for radiocontrast-induced nephropathy are more predisposed to having a worsened kidney function if furosemide is given before contrast administration than high-risk patients receiving gentle hydration before contrast exposure.

• Patients with a known history of urinary retention due to, for example, benign prostatic hyperplasia, neurogenic bladder with bladder evacuation abnormalities, or urethral and ureteral strictures should be observed closely during the initial days of furosemide treatment. After that, they require observation for worsening symptoms as excessive diuresis and urine retention can lead to acute urinary retention leading to acute kidney injury.

• The risk of hypokalemia increases with a high dose of furosemide, decreased oral potassium intake in patients with hyperaldosteronism states (liver abnormalities or licorice ingestion), or concomitant use of corticosteroid, ACTH, and laxatives.

• Furosemide at high doses, i.e., more than 80 mg per day, inhibits thyroid hormone binding to thyroid binding protein leading to a transient increase in free thyroid hormones that subsequently causes a mild decrease in total thyroid hormone.[28]

Monitoring

• Fluid status, BUN and creatinine to prevent oliguria and azotemia

• Obtain potassium before and during rapid diuresis

• Observe for signs of ototoxicity at the higher dose

• Clinicians should check the chart for fluid intake and output.

• Vitals: Orthostatic hypotension[29]

Toxicity with furosemide manifests as extensions of its diuretic activity. The main signs and symptoms of overdose with furosemide are blood volume reduction, dehydration, electrolyte imbalance, hypotension, hypochloremic alkalosis, and hypokalemia.[10]

Treatment of overdosage is supportive, and it consists of replacing excessive fluid and electrolyte losses. Clinicians should frequently determine serum electrolytes, arterial blood gas analysis, and blood pressure. In addition, providers must assure adequate drainage in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy). Hemodialysis does not accelerate furosemide elimination.

American Heart Association (AHA) estimated that there were 6.2 million people with HF in the United States between 2013 and 2016.[30] Managing patients with hypervolemia requires an interprofessional healthcare team depending upon the healthcare setting, outpatient vs. inpatient care. For symptomatic patients with hypervolemia secondary to any of the following conditions; heart failure, liver cirrhosis, or nephrotic syndrome/chronic kidney disease, patients usually need aggressive diuresis. Hospitalized patients requiring aggressive diuretics need care by an interprofessional team that includes a nurse, laboratory technologists, pharmacists, and clinicians, including advanced heart failure specialists.

Careful monitoring of the patient's clinical condition, daily weight, fluids intake, urine output, electrolytes, i.e., potassium and magnesium, kidney function monitoring with serum creatinine and serum blood urea nitrogen level is vital to monitor the response of furosemide. For example, if indicated for diuresis with furosemide, replete electrolytes lead to electrolyte depletion, and adjust the dose or even hold off on furosemide if laboratory work shows signs of kidney dysfunction. Similarly, patients who are on furosemide treatment in an ambulatory care setting need close monitoring to evaluate the response to treatment, intermittent electrolytes and kidney function monitoring to replete electrolytes and manage the dose of furosemide as indicated, and to assess for other adverse effects of the furosemide treatment and manage it accordingly.

While the clinician, NP, or PA will make the initial decision to treat with furosemide, the entire healthcare team must put forth an interprofessional effort to maintain therapy. Nursing will be on the front lines for inpatient or outpatient monitoring. They can also be the first to assess therapeutic effectiveness and watch for adverse drug reactions. Pharmacists should verify that dosing is appropriate, and to do so, they will need to have received renal and liver function testing results from the team. The pharmacist should also look for drug-drug interactions and alert the clinician or nurse if any are present. The pharmacy can also assist the clinician with therapy changes to address the braking phenomenon and ceiling effect. Clinicians can optimize furosemide therapy with a coordinated interprofessional team effort for positive patient results. [Level 5]

Review Questions

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