AUTHORS
Brian M. Pennington, MD, Assistant Professor of Emergency Medicine, Wright State University, Kettering, OH
Christopher M. Howell, DSc, MSc, MPAS, PA-C, MBA, Associate Professor, Kettering College Master of Physician Assistant Studies, Kettering, OH
PEER REVIEWER
Steven M. Winograd, MD, FACEP, Assistant Professor of Emergency Medicine, Mt. Sinai Medical School, New York City
Definition
End-stage renal disease (ESRD) is defined as overt renal failure requiring either dialysis or kidney transplant as a means of renal replacement therapy to maintain vital organ function.1-5 ESRD usually is the terminal stage of chronic kidney disease (CKD stage 5), although it can result from severe acute kidney injury (AKI). In addition, acute on chronic kidney disease stemming from volume depletion, such as with an acute illness or malnutrition, can require the use of renal replacement therapy.
Demographics and Epidemiology
ESRD is a rising health threat with a multifactorial etiology. CKD has a prevalence that reaches nearly 16% of the global population, with progression to renal failure estimated to be greater than 5%.6-10 CKD is associated with a myriad of comorbidities, including but not limited to diabetes mellitus, hypertension, and atherosclerotic vascular disease, which contribute to rising mortality burdens.
The risk of disease progression can occur from a direct renal insult to complications of systemic factors and progressive comorbidities. Recent population-based studies have cited a number of variables that make generalizability of disease risk an overwhelming challenge, including factors that are genetic, social, medical, and environmental.11
Risk Factors of Disease
The hazards for progressive renal function decline include genetic variances, racial predilection, and the presence of comorbidities. African-Americans have about twice the incidence of ESRD as the white population. This increased incidence is associated strongly with variants in the apolipoprotein L1 (APOL1) gene. Hypertension (HTN) is present commonly in patients with CKD, and is noted to be both a cause and a complication of renal impairment.7,12,13
Diabetes mellitus (DM), observed in 25% of patients with ESRD, plays a significant role in both the provocation of nephropathy and the perpetuation of disease progression to ESRD.1,13-15 Often, this is compounded by obesity and a multitude of other cardiovascular disease risks.13
Once kidney disease has been established, behavioral modifications are essential to reduce the risk for and the rate of progressive kidney function decline, yet numerous studies have supported both patient and iatrogenic neglect.10,16 Many patients with end-stage disease exhibit poor compliance to diet and exercise, regular screening intervals, and management for complex health conditions. Medical providers should gear management within the confines of clinical practice guidelines, involving appropriate blood pressure
(< 130/80 mm/Hg) and glycemic (HbA1c < 7%) goals.10,17,18 Acute illness can lead to poor oral intake and dehydration, which are risk factors for progressive kidney injury; however, a less common contribution to aggressive renal decline is a diet high in acidic foods and protein.4,13,17,19,20 Unfortunately, these dietary complications have a proclivity to those of a lower socioeconomic status, which also is correlated with advanced age and cardiovascular and established CKD.4,11
Given the complex nature of comorbid conditions, as well as the socioeconomic concerns contributing to patient compliance and the progression of CKD, a multidisciplinary approach may be appropriate early. This may include seeing a nutritionist and targeted care coordinators (certified diabetic educators) to reduce the risk of rapid decline.17
Making the Diagnosis
Most patients with early or stable CKD are asymptomatic.10,17 If symptoms are present prior to the progression to renal failure, these concerns often are vague and more consistent with causes of renal insult than a product of renal injury. Common symptoms encountered include depression and anxiety, fatigue, dyspnea, anorexia, xerostomia, nausea and vomiting, generalized pruritis and pain, restless leg syndrome, and edema.17 Making the diagnosis of CKD and ESRD requires laboratory confirmation. (See Table 1.)
Table 1. Stages of Chronic Kidney Disease |
||
|
Chronic Kidney Disease Stage |
Description |
Possible Signs and Symptoms |
|
1 |
Kidney damage with normal kidney function |
High blood pressure, swelling in legs, urinary tract infections, or abnormal urine test |
|
2 |
Mild loss of kidney function |
|
|
3 |
3a: Mild to moderate loss of kidney function 3b: Moderate to severe loss of kidney function |
Low blood count, malnutrition, bone pain, unusual pain, numbness or tingling, decreased mental sharpness, or feeling unwell |
|
4 |
Severe loss of kidney function |
Anemia, decreased appetite, bone disease, or abnormal blood levels of phosphorus, calcium, or vitamin D |
|
5: End-stage renal disease (ESRD) |
Kidney failure and need for transplant or dialysis |
Uremia, fatigue, shortness of breath, nausea, vomiting, abnormal thyroid levels, swelling in hands/legs/eyes/lower back, or lower back pain |
CKD and the progression of disease is associated with a decreasing glomerular filtration rate (GFR) and increasing albuminuria.7,8,21 In most clinical circumstances, the GFR is estimated (termed eGFR) using the patient’s age, gender, ethnicity, and serum creatinine applied to validated formulas rather than directly measured by collecting a 24-hour urine sample. ESRD is defined by an eGFR < 15 mL/min/1.73 m2.2,5 However, albuminuria also is independently associated with mortality and ESRD.21 In fact, both declining eGFR and the rising albuminuria can independently predict progression to ESRD, as well as cardiovascular outcomes.14,21 Microalbuminuria in the diabetic patient does serve to indicate the disease progression of CKD, but it does not predict overt renal failure in this population.2
Once CKD of any stage is discovered, maximization of dietary management, pharmacologic therapy, and patient education should be initiated to slow progression of disease.13 On the other hand, ESRD requires more aggressive management with either dialysis or kidney transplant to maintain vital organ function.1-3 A living kidney donor is superior to dialysis, but candidacy for both of these interventions is a multi-dimensional consideration, including comorbidities and socioeconomic factors of the patient and the donor.22
Within the emergency department (ED), identification of CKD requires more of a targeted management strategy. Certainly, an established diagnosis of CKD will aid in the diagnosis and management of the patient, and evaluation should focus on acute exacerbations or emergent complications of chronic disease.
Complications Related to Vascular Access
There are several options for vascular access to perform hemodialysis, but clinical experience supports a native arteriovenous fistula (AVF) as superior in hemodialysis efficiency.23,24 The superiority of the AVF is most evident once fistula sites have reached a state of “maturity,” with reported longer patency and fewer complications than those compared to AVF grafts and central venous catheters.23,24 While efforts are made to reduce complications and overall risk, complications do occur. In fact, of those patients with complications, including steal syndrome, infection, stenosis, thrombosis, aneurysm, and hemorrhage, more than 40% had to be hospitalized.23,24
There are two methods to access the AV fistula or graft: the rope ladder and the buttonhole approach. The rope ladder technique rotates needle sites with each hemodialysis (HD) treatment, while the buttonhole technique uses the exact same spot, at the same angle, and at the same depth of penetration every time. With time and repeated cannulations, a scar tissue tunnel track develops, enabling the subsequent use of blunt needles for cannulation and dialysis.
There are pros and cons to each technique. The rope ladder technique tends to have a lower rate of infection, while the buttonhole technique has been shown to reduce cannulation discomfort, increase cannulation ease, and involve fewer incidences of hematomas, access interventions, and aneurysm formations. The major disadvantage of the buttonhole technique is that to be effective it requires the same cannula to cannulate the access each time.
Steal Syndrome
Symptomatic steal syndrome has a reported occurrence rate of 1-2% for distal extremity fistulas and between 5-10% in proximal extremity fistulas.25 Those with peripheral vascular disease, a condition more common in elderly patients, smokers, and those with DM, are more likely to be affected. A matured AVF can lead to a reduction in blood flow distal to the AV anastomosis producing hypoxia, ischemia, and necrosis of the tissue.26
The symptoms and presentation of steal syndrome are variable. Early in the disease, overt or classic symptoms often are lacking.27 Nonetheless, as the disease persists, there often will be complaints of claudication progressing to persistent severe pain even without provocation, often distal to the AVF site.26,27
Signs may include skin mottling, and the affected extremity may be cool to the touch.27 The distal extremity also may be found to be insensate and exhibit loss of gross and fine motor movement (paralysis), and it may not demonstrate a palpable pulse.26,27 Without prompt intervention, the terminal aspect of this injury pattern is irreversible tissue necrosis.27 An interesting pathognomonic finding for steal syndrome is a return of a distal pulse with compression of the dialysis access site.26,27 A point-of-care ultrasound may show a marked reduction or even reversal of flow through the arterial segment distal to the AVF.
Emergent management of steal syndrome is somewhat limited because definitive management requires ligation of the arteriovenous access by a vascular surgeon.27 The urgency of the consultation depends on the severity of the condition and clinician judgment.27
Hemorrhage
Hemorrhage in the hemodialysis patient may arise from platelet dysfunction, anticoagulation medications, or problems with the fistula itself.27 Infection also has been observed as a risk factor for bleeding since bacterial involvement weakens vascular wall integrity.28 Even if it is remote, a previous hemorrhage is a risk factor for AVF hemorrhage.28
Although challenging, it usually is possible to control hemorrhage from an AVF using one of several techniques. Applying direct pressure remains the primary intervention for controlling hemorrhage from a bleeding AVF. It is recommended that the clinician locate the exact source of bleeding and apply direct pressure for at least five to 10 minutes. If bleeding is controlled, it is recommended that the patient be monitored for approximately one to two hours to ensure no recurrence.27,28 Although it is difficult to determine how much pressure is being applied, excessive pressure should be avoided because it can cause iatrogenic fistula thrombosis.28
If direct pressure does not yield hemostasis, topical hemostatic agents may provide equal benefit. For example, Gelfoam is a water-insoluble, porous material prepared from purified pork skin gelatin, granules, and water that acts as a physical matrix to facilitate clot formation. It can be applied directly to the bleeding site and maintained until hemostasis is achieved.27 If additional pressure is required, a bandage can be applied directly over the product.
Recombinant human thrombin (rhThrombin) may be used in conjunction with Gelfoam if additional hemostatic support is needed. Thrombin activates factors V, VIII, XI, XII, and fibrinogen, facilitating both intrinsic and extrinsic pathways of the coagulation cascade.
Another option is Surgicel, which is an absorbable hemostatic agent composed of an oxidized cellulose polymer framed similarly as a gauze material that can be applied directly to the bleeding site to aid in hemostasis.27
Tranexamic acid (TXA) inhibits fibrinolysis by displacing plasminogen from fibrin. TXA can be applied as a solution to gauze or other dressings or as a paste created by mixing a small amount of water with TXA powder and applying directly to the site of bleeding.29
If the patient is taking an anticoagulant, then standard protocols for anticoagulant-induced hemorrhage should be followed.
If the above interventions have failed to achieve hemostasis and the AVF has matured (gauged in months), placing a suture may help control bleeding. It is reported that after several months, the skin and subcutaneous tissue is adherent to the graft; therefore, a figure-of-eight suture placed superficially at the skin puncture site may control bleeding and prevent an expanding hematoma.27,28 It is suggested that before placing the suture, having an assistant hold pressure to occlude the vessel proximal and distal to the bleeding site until bleeding stops will help to further reduce complications and improve tolerance to suture placement.27
Infection
Infection of the hemodialysis patient’s vascular access is a significant cause of morbidity and mortality. The estimated rate of infection is between 1 in 50 to 1 in 20 patients (2% to 5%) per year with an AVF, with the greatest risk observed consistently in DM patients.30 Conversely, a 5-18% rate of infection in catheters and 11-20% rate of infection in AV grafts has been reported, indicating a lower infection rate in AVFs, yielding comparable complication rates.25
Infections can consist of seemingly mild perivascular cellulitis and soft-
tissue cellulitis to more serious infections of an aneurysm, hematoma, or even expanding abscess requiring surgical drainage.30 Chronically uremic hemodialysis patients experience an altered immune response and may escape detection, and frequently they may not exhibit classic inflammatory findings in the area of the AVF.27,28,30 Rather, such patients may present with nonspecific fever, general malaise, leukocytosis, and/or hypotension, and an AVF with surrounding tissue that is firm with palpation. For these indeterminant findings, point-of-care ultrasound should be used to delineate if there is evidence of an infected thrombus or infected fluid collection necessitating surgical management. Common organisms observed in these cases include Staphylococcus aureus, Staphylococcus epidermidis, and gram-negative bacteria.27,30
If there is a concern for AVF infection, blood cultures should be drawn, and patients should be treated with intravenous antibiotics. Vancomycin should be a first-line agent given the proclivity for S. aureus infection. Nonetheless, polymicrobial risks still occur. If broader coverage is desired, then gentamicin should be considered for any suspected gram-negative involvement. These patients should be hospitalized until culture and sensitivity results return and antibiotics can be tailored.26,27,30
Stenosis and Thrombosis
The most common complications of AVFs include stenosis and thrombosis, which have been reported in nearly half of HD patients, with an increased risk associated with central venous dialysis catheters (thrombosis).26,27 Symptoms of upper extremity AVF stenosis may include edema and discomfort in the ipsilateral upper extremity and chest wall.26,27,30 Additionally, cannulation into a stenotic vein poses unique challenges, including intolerance and decreased quality of HD treatments. Patients also experience prolonged bleeding after puncture of the AVF, which may require careful measures to control.26
Physical exam findings depend on the location of the narrowed segment and whether the inflow or outflow of the AVF is stenotic.26,27,302 If the inflow segment is impaired, then the patient typically will have a diminished distal pulse (usually the radial artery) and a high-pitched bruit at the site of stenosis. On the other hand, if the outflow segment is stenosed, then there will be a bounding pulse and an absence of a palpable thrill distal to the affected segment.27
Doppler ultrasound should be performed to assess blood flow.27 Angiography also may be required to determine the degree of stenosis. Vascular surgery should be consulted as well, since percutaneous transluminal angioplasty can improve and prolong AVF function.26
AVF thrombosis often occurs with venous outflow stenosis imparting resistance to blood flow and promoting stasis. Hemodialysis is a recognized risk factor for fistula thrombosis because repetitive cannulation directly traumatizes the endothelium, compression of the access site frequently occurs, and the relative hypovolemic state of HD patients is commonplace.26,27 Additionally, erythropoietin prescribed for patients with chronic anemia from ESRD increases levels of acute phase reactants and leads to chronic inflammation, which further increases the risk of thrombosis.26
Patients with an AVF thrombosis often complain of pain, discomfort, or edema around or distal to the fistula. On clinical examination, the thrombus may be palpated at the AVF site but should not be regarded as a diagnostic finding.26,27 Fistula thrombosis also can be identified by the absence of auscultatory bruit and palpable thrill, although ultrasound often still is required to confirm the diagnosis through direct visualization of the hyperechoic obstruction and lack of compressibility.27
With an AVF thrombosis, vascular surgery should be consulted emergently. Treatment options that frequently are explored include thrombectomy, thrombolysis, and possibly angioplasty.27
Aneurysm and Pseudoaneurysm
Aneurysms form in AVFs because of vessel wall weakening in response to repetitive cannulations. Aneurysmal dilation also can occur naturally over time due to a high blood flow rate and high pressure within the fistula. The rate of aneurysm formation has been reported to be about 1.5% per year or 0.04 per 1,000 patient days.25
Symptoms of aneurysms range from an expressed cosmetic concern, described as a “large and unsightly” vascular prominence, to high-output heart failure, or even aneurysm rupture. Patients may experience pain in the affected extremity, neurologic dysfunction caused by the aneurysm impinging on surrounding nerves, thinning of the skin overlying the fistula, or even hemorrhage resulting from skin erosion.25
Pseudoaneurysms are pulsatile extravascular hematomas resulting from AVF access sites. Although pseudoaneurysms are not as critical as aneurysms, patients with pseudoaneurysms may present with symptoms of hemorrhage or concerning for infection.27
Doppler ultrasound should be used to identify and differentiate aneurysms and pseudoaneurysms from other fistula abnormalities.25
Although aneurysmal ruptures are unlikely events, they are significant. The risk of rupture dramatically increases if the area of the aneurysm is traumatized, as when the rope ladder technique is used for access.25-27
Treatment is guided by the expressed symptoms and the need for future dialysis treatments. If the patient is asymptomatic and HD no longer is required, or if the patient is bothered by the appearance, surgical excision and ligation may be indicated.23 In symptomatic patients or those with associated complications, improperly treated aneurysms are at risk of rupturing, causing life-threatening hemorrhage. Additionally, this may cause limitations in available sites for future cannulation.25 Therefore, vascular surgery should be consulted because surgical repair may be indicated.
Complications Related to ESRD
Pericarditis and Pericardial Tamponade
Pericarditis is common in those with ESRD, often as a product of either uremia or hemodialysis.31 Uremic pericarditis occurs when pericarditis presents on initiation of renal replacement therapy or within eight weeks of initiation; after eight weeks, it is termed dialysis pericarditis.31 The accumulation of toxic metabolites, nitrogenous metabolic end products, and alterations in fluid, electrolyte, and acid-base hemostasis are contributing factors in uremic pericarditis.31
Dialysis pericarditis is reported most commonly in those with missed or inadequate dialysis treatments, although the incidence of pericarditis approaches 20% in patients on chronic hemodialysis.27,31 The classic signs of pericarditis often are observed as anterior chest pain that is worse with inspiration, improved by sitting forward, and worsened when supine, as well as the presence of pericardial friction rub.31
Uremic pericarditis can present differently than acute non-uremic pericarditis. Uremic pericarditis has a tendency toward a more indolent course, often lacking the pleuritic chest pain or positional chest pain associated with non-uremic pericarditis.27
The initial evaluation should assess for other causes of chest pain using ancillary testing with electrocardiogram (ECG), chest X-ray, laboratory studies, and potentially bedside ultrasound or computed tomography (CT) imaging. Of note, leukocytosis and fever are not seen consistently in uremic pericarditis.27 Additionally, the ECG changes often associated with non-uremic pericarditis (diffuse ST-elevation and PR depressions) have been reported as low as 60% in uremic pericarditis, and, therefore, should not be expected with this disease.31,32 For these reasons, diagnosing uremic pericarditis frequently is a challenge.32
Bedside echocardiography can be of great value if pericarditis is suspected. It should be noted that pericardial effusion is quite common in patients with ESRD on dialysis, even in asymptomatic patients. Therefore, its presence or absence should not be regarded as diagnostic.31 However, pericardial tamponade is a life-threatening complication of uremic and dialysis pericarditis, occurring in as many as 20% of patients. The presentation of pericardial tamponade can be precipitated by hypovolemia or dysrhythmia, although hemorrhage into the pericardium also has been observed.31
The clinician should be vigilant and look for physical examination findings supportive of tamponade, including hypotension, tachycardia, jugular venous distention (JVD), and pulsus paradoxus. If performed early, bedside ultrasound will show pericardial fluid (see Figure 1) and frequently will reveal right atrial systolic collapse, while right ventricular diastolic collapse has a higher specificity for tamponade.33 Additional findings include a plethoric inferior vena cava with minimal respiratory variation. (See Figure 2.) A surrogate marker for pulsus paradoxus is noted by exaggerated respiratory cycle changes in mitral and tricuspid valve in-flow velocities.33
Volume resuscitation in the hypovolemic patient may have significant benefit. However, in the euvolemic or hypervolemic patient, IV fluids could precipitate or worsen tamponade, so IV fluid therapy should be considered on a case-by-case basis.31
Figure 1. Point-of-Care Echocardiogram |
 |
|
Subcostal view of the heart demonstrating a pericardial effusion (arrow). |
Figure 2. Point-of-Care Echocardiogram |
 |
|
Probe is in the subcostal location with the marker oriented cranially to view the heart and IVC. The arrow indicates pericardial effusion with plethoric IVC visualized. |
The most effective treatment for uremic and dialysis pericarditis is to begin dialysis treatment if not already initiated, or to intensify treatment if the patient already is on dialysis.34,35 Assessing the success of treatments may be challenging. However, improvement in symptoms, resolution of pericardial effusion, and resolution of pericardial friction rub are reported goals of therapy.34,35
Additional therapeutic considerations include aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, and corticosteroids in those patients who do not respond adequately to dialysis. Corticosteroids may be reserved for those patients unable to take NSAIDs.31,34,35 Colchicine is contraindicated in patients with pericarditis and severe renal impairment, and therefore should be avoided in this patient population.31 Aspirin and NSAIDs can lead to bleeding in dialysis patients who are already at higher risk for hemorrhagic complications.
Treatment options for pericardial tamponade include pericardiocentesis or possibly pericardial window depending on the severity and response to treatment.31,34,35
Anemia
Anemia develops in more than 90% of patients with CKD, occurring as early as Stage 3b (< 30 mL/min eGFR).17,36 This is due in large part to direct erythropoietin deficiency, failure of the red blood cells (RBCs) to survive, and uremic toxins impairing the role of erythropoiesis.36 ESRD patients are treated commonly with the erythrocyte-stimulating agent (such as epoetin alfa) to stimulate the production of red cells. This is not without potential harm, as mortality increases have been observed with erythrocyte-stimulating agent (epoetin alfa) excesses.36 Patients should be evaluated for signs and symptoms of acute hemorrhage, hypovolemia, or symptomatic anemia necessitating blood transfusions.
Hyperkalemia
As renal function declines, toxic uremic solutes often will accumulate in the plasma, bearing mixed pathophysiologic mechanisms for mortality risks.5,37 The renal system plays a vital role in potassium regulation, as evidenced by gross derangements consistently observed in those with CKD, including ESRD.38-40 When the glomerulus is unimpeded, the renal system will excrete and filter more than 800 mmol of potassium daily.13 Given the reduced GFR associated with ESRD, hyperkalemia is one of the most common findings warranting emergent management.38,40
The risk of mortality from cardiac dysrhythmias certainly can occur at values > 6.0 mEq/L. However, there is no predictive threshold value of imminent threat in those who have CKD.38,40 For example, patients with advanced age (particularly > 80 years of age) and those with chronic hyperkalemia seem to tolerate high levels of serum potassium with little evidence of cardiac impairment, presumably due to the cardiac membrane having a reduced sensitivity to potassium instabilities.38,39 Additionally, elevated levels of serum calcium that may be observed in ESRD patients actually reduce the effect of potassium on the resting membrane potential.38 For this reason, the risk of dysrhythmia depends on the rate of change in serum potassium more than on the serum level.41
Despite the lack of consistent correlation between potassium levels and a predictable physiologic manifestation of disease, all-cause mortality has been observed consistently in populations with serum potassium levels that exceed 5.0 mEq/L.39 Yet, Green and colleagues have argued that potentially fatal values in individual patients are not achieved until in excess of 6.0 mEq/L, with near certainty of fatality when levels are greater than 7.5 mEq/L without prompt treatment.38
Hyperkalemia has been associated with a multitude of dysrhythmias, notably bradydysrhythmias to ventricular dysrhythmias, pulseless electrical activity (PEA), and asystole.38 The earliest observable change is the peaked symmetric T waves in the precordium (namely V2-4) and a narrow base.38 (See Figure 3.) Following this, the atria are affected next, with a prolongation of the PR interval prior to a progressive flattening of the P wave, which historically has been observed when serum levels rise to 7.5 mEq/L.
Figure 3. Electrocardiogram of a Patient With Hyperkalemia |
 |
|
Electrocardiogram of a patient with hyperkalemia demonstrating peaked T waves and prolonged PR interval. K+ was 6.8 mEq/L. |
Natural progression of the clinical course ultimately will affect the ventricles, widening the QRS complex.38 If the potassium level continues to rise, the risk becomes far graver so that by 7.0-8.0 mEq/L, the QRS complex will widen and begin to morph into a shared wave with the T wave, forming what is known as the sine wave. (See Figure 4.) Without intervention, cardiac arrest from ventricular fibrillation is imminent.38
Figure 4. Electrocardiogram of a Patient Presenting With a Sine Wave Associated With Severe Hyperkalemia |
 |
|
Electrocardiogram of a patient with a potassium level of 7.8 mEQ/L presenting the “sine wave” associated with severe hyperkalemia. |
Generally, treatment of hyperkalemia requires a multifaceted approach, including prevention of imminent cardiac collapse, correction to what is deemed a physiologically stable level, and removal of excesses potassium.41 Stability of the cardiac membrane requires the use of calcium infusion in an effort to prohibit fatal dysrhythmias.41 If a patient currently is taking digoxin and there is concern for digoxin toxicity, calcium infusion has a theoretical risk, but one not observed in clinical practice.42 The authors recommend 10-30 mL of 10% calcium gluconate (4.6 mEq/10 mL) provided over 10 minutes, as this can be administered in a peripheral line with minimal caustic risk.40 (See Table 2.)
Table 2. Therapy Options for Hyperkalemia |
|||
|
Medication |
Recommended Dose |
Administration |
Onset of Action |
|
Calcium |
10 mL calcium chloride or calcium gluconate (10%) |
IV |
Immediate 1-3 minutes |
|
Insulin (short-acting) |
5 to 10 units |
IV |
20 minutes |
|
Albuterol |
10 to 20 mg |
Inhalation |
30 minutes |
|
Furosemide |
40 to 80 mg |
IV |
15 minutes |
|
IV = intravenous |
|||
Calcium chloride (13.6 mEq/10 mL) also may be considered when available and could be used temporarily through peripheral access. The risk of venous sclerosis (thrombophlebitis) suggests this should be used only in the emergent setting and for as limited a time as possible.40 Both have an onset of action that is reportedly less than three minutes and a duration that is between 30 minutes and one hour.40
The most effective immediate interventions for altering potassium levels involve intracellular potassium shifts. Beta-agonists and insulin have synergistic effects when administered simultaneously.40,41 An example of this would be the administration of 10 to 20 mg of nebulized albuterol over 10 minutes and 10 to 20 units of regular insulin IV bolus ordered simultaneously or in close succession.40 The insulin is provided only after the administration of one (25 g) to two amps of IV 50% dextrose solution (D50) as a bolus or IV infusion to avoid hypoglycemia, and serum glucose should be monitored every hour for up to four to six hours after IV insulin has been given.40,43
If a non-gap metabolic acidosis also is present, then a 50 to 100 mEq IV bolus of sodium bicarbonate (NaHCO3) also may be administered. This causes a transcellular shift and excretion of potassium out of the distal nephron via potassium channel upregulation and may offer some cardiac protection from the acidosis.40,41
The best means to eliminate excess potassium in the CKD patient is with dialysis.41 In fact, HD has been demonstrated consistently to be the most effective resource in the treatment arsenal, particularly for the renally impaired, demonstrating a decrease of 2 mmol/L by three hours post-treatment.40 Peritoneal dialysis (PD) is an option for some patients, but it should be reserved for those who can tolerate a more modest reduction, as this method is consistently slower.40 PD lends itself as a reasonable treatment option in resource-attenuated environments. However, PD has the limitation of requiring knowledge of placement and materials that are unique to this approach and may not be suitable for all clinical scenarios.44 Nonetheless, it should be considered a safe alternative for those with an urgent need for HD, especially when temporary vascular access risks catheter-associated bacteremia, vascular stenosis, and protracted hospitalizations that are a prevailing health concern.45
Where HD or PD is impractical but elimination still is preferred, then urine and fecal elimination are considered acceptable alternatives. Loop diuretics are effective, but generally require a preserved renal function to be used safely.41 Therefore, in oliguric patients and those with known ESRD, this is not recommended. Use of sodium polystyrene sulfonate (Kayexalate), a chelating agent, is discouraged because of a delayed onset of action and poor side effect profile.41 Additionally, there are concerns for gastrointestinal necrosis as well as an increased sodium burden associated with this therapy, which only complicates an already challenging clinical course.41
Although there is proposed promise in novel agents, such as patiromer (Veltassa) and sodium zirconium cyclosilicate (ZS-9), that more selectively bind the potassium, their use is discouraged in the emergency setting.40,41 Reportedly, studies have only quantified benefits in the outpatient setting in those patients with serum potassium < 6.5 mEq/L and not in those with ECG changes when using patiromer.41 Although the AMETHYST-DN study validated the use of this agent in moderate to severe renal disease, it was limited to outpatient care and specifically while patients were being treated with renin-angiotensin-aldosterone system blockade.18,46,47
Hypokalemia
Hypokalemia long has been observed in dialysis patients, but the findings often are associated more with poor nutrition, diuretic use, and comorbidities.39 Although the prevalence is less common than hyperkalemia in those with CKD, low potassium is known to have adverse effects on the resting membrane potential of the myocardium, leading to ventricular dysrhythmias.39 Less appreciated are the direct renal effects, including direct interstitial scarring and “renal fibrosis via modulation of renal inflammation and local activation of the RAAS,” which can perpetuate CKD to ESRD.39 Although dysrhythmias are likely to occur when potassium levels decline below 4.0 mmol/L, much like hyperkalemia, there are threshold values for serum potassium and the development of the aforementioned dysrhythmias.39
Potassium repletion can be accomplished via oral (PO) and/or IV administration with variable levels of tolerance. It should be noted that hypomagnesemia, if present, must be addressed for hypokalemia treatment to be effective, with IV magnesium typically well-tolerated.48 Generally, 10 mEq of KCL will increase serum potassium by 0.1 mEq/L. When given PO, a more generous dosing strategy may be employed, but this requires that the patient be able to swallow a large pill. Liquid medications can be used if patients can tolerate the flavor. IV replacement has been associated with a burning irritation that occurs at the IV site and can be given at a rate no more than 10-20 mEq/L per hour.
Hyperphosphatemia and Hypocalcemia
Hyperphosphatemia and hypocalcemia from secondary hyperparathyroidism often are observed in CKD and ESRD patients.5,20 These serum manifestations are associated with what is commonly referred to as the chronic kidney disease-mineral and bone disorder (CKD-MBD) pathway, which together is connected with appreciable mortality increases in those with ESRD.13,20 Hyperphosphatemia is the most salient contributing factor of CKD-MBD leading to cardiovascular insult, yet there is little acute risk associated with the majority of patients in the ED.13,20
Commonly, this pathway is associated with long-standing CKD patients, and while management may be initiated in the ED, CKD-MBD is more of an insidious progression and often does not render the same threat of cardiac instability observed in potassium derangements. Most of the symptoms associated with hyperphosphatemia alone include those of arthralgias and pruritis developing over years. It is unlikely to be associated with any acute development, and therefore rarely requires emergent intervention.13,20
Dialysis Disequilibrium Syndrome
Dialysis disequilibrium syndrome (DDS) is a rare, serious, yet poorly understood complication affecting the central nervous system in patients during or after completion of hemodialysis.49,50 It is thought to be due to cerebral edema and increased intracranial pressure stemming from the extraction of urea at a rate that exceeds equal measure from the brain.49-51 The symptoms are expressed in a spectrum and may include headache, nausea, and restlessness that progress to confusion, coma, and even death.49,51 Although rare, this syndrome has been associated with patients with severe azotemia who receive initial hemodialysis.49,51
DDS usually is mild, transient, and self-limited. DDS is diagnosed using clinical criteria. It is mostly a diagnosis of exclusion of other causes, such as hypoglycemia, hypocalcemia, hypercalcemia, hyponatremia, subdural hematoma, or stroke. Most patients will recover after a period of observation and gentle isotonic IV fluid administration.
In severe cases, treatment is geared toward reducing intracranial pressure using mannitol or hypertonic saline to raise blood osmolality. Mechanical hyperventilation also has been used.50 Prevention is desirable; however, the mechanism of disease development remains unknown, so predicting which patients are at risk remains a challenge.49,50 Blood urea nitrogen (BUN) in excess of 175 mg/dL has been shown to be a risk factor for rapid decline in patients with DDS.51 Additionally, those deemed vulnerable to central nervous system (CNS) disease as well as electrolyte derangements and liver disease also are at risk of exhibiting this condition.51
Dialysis and Mortality
Irrespective of the cause for declining renal function, ESRD and death are significantly greater in those with CKD than in the general population.14 For those with ESRD, particularly from progressive CKD, the most effective treatment is a living donor transplant.22 However, this is neither appropriate nor practical for all patients with ESRD.
Although much in the literature validates mortality reduction when dialysis is administered in those with ESRD, the optimal timing for the implementation of this therapy remains an area of question and a potential area of further study.52 Despite these limitations, early management with nephrology consultation at a minimum is the standard of care since a delay in initiating dialysis in those deemed appropriate candidates will increase mortality exponentially.53
Conclusion
ESRD is defined as overt renal failure requiring either dialysis or kidney transplant as a means of renal replacement therapy to maintain vital organ function.1-3 Many factors contribute to this rising global health concern, including an aging population.4,6-11,19 Yet, factors that often are underappreciated are those associated with genetic and racial factors, as well as salient comorbidities such as HTN and DM.1,14,15,19,38,54 Although ESRD is widely accepted as a terminal variant of CKD, AKI associated with renal failure frequently is observed in the ED. Compounding the clinical challenge is the fact that there are no symptoms or physical examination findings associated with certain disease in those affected.10,16,17
Significant morbidity and mortality are associated with complications of ESRD, including pericarditis, pericardial effusions and tamponade, uremia, anemia, electrolyte disturbances, and cardiac dysrhythmias. Additionally, the AVF and AV grafts used to perform hemodialysis are associated with their own complications that require emergent medical treatment. Evaluation and management of patients with ESRD and patients on hemodialysis can be challenging because they are at risk for a multitude of imminently life-threatening complications.
The initial focus should be on the evaluation and management of the ABCs (airway, breathing, and circulation) of the patient. Providers should use proper laboratory and imaging studies as well as ECGs to further evaluate for electrolyte disturbances and other metabolic cardiac sequelae of disease. Interventions for AKI and ESRD should be employed early to prevent imminent cardiac collapse. Such interventions may include targeted symptomatic therapy and renal replacement therapy, including HD. In large part because of logistical delays in providing dialysis, treatments meant to stabilize the patient often are required but do not provide the same long-term benefits in morbidity and mortality reduction. Such interventions include symptomatic therapy (antiemetics) and IV fluids, in addition to electrolyte stabilizing methods appropriate for ED management. One should consider early involvement of consultants including nephrology and/or vascular surgery as clinically indicated. The clinician must consider the social and physical health constructs affecting each patient and provide appropriate emergency management while definitive interventions are coordinated.
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Evaluation and management of patients with end-stage renal disease and patients on hemodialysis can be challenging because they are at risk for a multitude of complications.
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