An overview of renal failure & considerations for treatment
Among critically ill and injured patients, maintaining homeostasis and preserving adequate organ function is always the primary objective of our care. However, the sequela of our most frequently encountered disease processes can greatly impact this goal.
When derangements in homeostasis progress to organ dysfunction, patients can quickly become critically ill, with steadily increasing mortality rates. One of the first systems to derail because of critical illness are the kidneys. When renal dysfunction occurs as a result of an acute illness, an experienced, multidisciplinary team may be needed to effectively care for these patients.
In many instances, these patients require very specialized critical care teams and advanced renal replacement therapies (RRTs) that can only be offered by tertiary and quaternary care centers. Most patients don’t initially seek medical attention from one of these large, academic centers usually located in urban areas. The initial stages of these patients’ care are provided at outlying community hospitals.
The patients’ illnesses have either progressed to a point where they’ve exhausted the resources and expertise available at the community hospital, or the patient was initially stabilized and prepared for transfer to one of these major centers at a later time.
Regardless of the path taken, EMTs and paramedics will be called to bring their expertise to the table and assist in moving these critically ill and complex patients from one hospital to another. In this article, we’ll discuss the causes of acute kidney injury (AKI), its clinical features, progression and indications for advanced therapies.
Diagnosis, Pathophysiology, & Incidence
The renal system stands at nearly the top of the list of organ systems most often impacted by the course of a critical illness. The kidneys are extremely susceptible to even subtle changes in homeostasis.
In the acute phases of a patient’s illness, this decrease in kidney function is known as AKI, formally called acute renal failure. The name change was necessitated by the fact that a decrease in the kidneys’ ability to clear waste didn’t equate to absolute organ failure. In addition, most cases of AKI are transient if the reversible causes are treated early.
The diagnosis of AKI is made when the kidneys are unable to clear the buildup of nitrogenous waste from the body at a normal rate. The buildup of these waste products is best observed by the measurement of a patient’s serum creatinine. The criteria for diagnosis is having at least one of the following: 1) A rise in serum creatinine of at least 0.3 mg/dL over the baseline in a 48-hour period; or 2) A rise in serum creatinine of at least 1.5 times the baseline creatinine over the previous seven days.1 A third criterion that utilizes urine output as a diagnostic trigger isn’t often used because certain circumstances can confound its reliability.2 That said, a sudden or progressive decline in urine output should still warrant the suspicion of renal impairment.
Classically, renal dysfunction is categorized based on where the causative injury to the kidney(s) originated and which part of renal anatomy is most directly impacted. The causes of AKI are categorized into three groups:
1. Pre-renal. Pre-renal insults primarily focus on disease processes that affect renal perfusion. The pathogenesis of pre-renal AKI can include true volume depletion (e.g., excessive vomiting/diarrhea or diuretic overdose), hypovolemia from hemorrhage, other shock states, cardiorenal syndrome (i.e., heart failure), and hepatorenal syndrome (i.e., liver failure).
Volume depletion and hypovolemia inhibit renal perfusion due to an overall lack of circulating blood volume. Conversely, other forms of shock, cardiorenal syndrome and hepatorenal syndrome cause decreases in the kidney’s pulsatile perfusion due to impaired blood circulation. In nonhemorrhagic shock and cardiorenal syndrome, blood isn’t able to be effectively propelled through the kidney’s vasculature. In hepatorenal syndrome, the kidneys become bogged down by an inability to clear venous blood volume due to portal vein hypertension.
2. Intra-renal. AKI from intra-renal pathologies lead to renal impairment by injuring the renal tissue directly. The intra-renal processes that lead to AKI are differentiated based on which parenchymal tissue is affected: renal vasculature (e.g., malignant hypertensive crisis, hemolytic uremia), glomeruli (e.g., IgA nephropathy, lupus), and renal tubules (e.g., nephrotoxin exposure, sepsis).
3. Post-renal. Post-renal causes are due to obstructive urinary stasis that ultimately results in hydronephrosis. The obstruction is usually a result of progressive prostate diseases (e.g., benign prostatic hyperplasia or malignancy) or other metastatic disease.
It’s important to note that, despite how a particular cause of AKI is categorized, its effects can progress to another component of the renal anatomy. For instance, prolonged hypotension, which is pre-renal in origin, can cause acute tubular necrosis, which is intra- renal. This crossing of etiologies demands astute clinical attention to the root cause. Although the majority of AKIs are reversible, the longer an AKI persists and progresses, the greater the likelihood the injury will lead to permanent damage.3
Given the wide range of causative factors that can lead to the development of an AKI, it’s not surprising that AKI is one of the more common complications of critical illness. Of all patients hospitalized, nearly 10% will develop some degree of AKI.4 The incidence soars to more than 50% for intensive care patients.5
For nearly 70% of these patients, the etiological category is pre-renal and/or acute tubular necrosis (ATN).6 This is likely due to the prevalence of sepsis in this patient population.
Among critically ill and injured patients, the most common cause of AKI is sepsis.7. There are several reasons for this, many of which aren’t yet fully understood. However, it’s currently thought that the impact sepsis has on blood pressure causes the decrease in renal perfusion, thus causing the pre-renal injury. It’s also thought that sepsis provokes ATN by damaging the renal tubules as a result of persistent hypoperfusion. Inflammatory mediators released in huge quantities during the sepsis disease process cause damage that, in turn, worsens the ATN.
In the majority of cases of AKI, there’s little to no clinical manifestation of the AKI itself, especially in the early phases. Patients often seek medical attention for the underlying causes of the AKI: sepsis, diabetic ketoacidosis, surgery, trauma, etc. However, regardless of the cause, AKI represents a serious and potentially life-threatening complication of any critical illness.
In the initial, hyperacute phases of AKI, the goal is treating the reversible causes, such as hypovolemia/hypotension, hypervolemia and urinary retention.
In most cases, the cause of AKI isn’t transient. For instance, sepsis and cardiorenal/hepatorenal syndromes can take days or weeks to overcome and return to a near-baseline status. In those cases, care teams will focus on maximizing the patient’s hemodynamics and overall clinical condition in order to preserve as much renal function as possible.
In many critically ill patients, the AKI will continue to progress despite renal- protective measures. In these patients, the AKI can become very dangerous and its complications can become life-threatening. Once the AKI has progressed to this point, surveillance for and treatment of the immediate life threats become the focus. In persistent AKIs that have progressed to a moderate or severe course, there are four immediate life threats that warrant providers’ attention:
1. Volume overload: In the most basic generalizations, AKI represents an ineffective ability of the kidneys to clear excess water from the body. This is quite problematic, since most critical care patients have a positive volume status. This is especially true with septic patients, due to the volume expansion that occurs during the initial resuscitation, as well as the constant obligate fluid intake due to antibiotic therapies, electrolyte management, intravenous medication administration, blood products and enteral/parenteral nutrition.
Hypervolemia presents a host of unique challenges. Patients with known heart disease can become susceptible to systolic dysfunction, worsening the volume status and AKI by way of cardiorenal syndrome. Pulmonary congestion from hypervolemia can also cause acute lung injury, another life-threatening complication of critical care patients.8,9
Volume overload can pose not only an immediate threat to a patient’s life, but it can also have long-lasting effects on post-recovery morbidities. Aggressive treatment and planning must be undertaken at the first indication that an AKI is developing in the presence of volume overload. Therapy should center on loop diuretics. An initial load of furosemide 40-80 mg IV can be given. If urine output doesn’t respond after an hour, a second dose of furosemide is given at twice the strength of the first.
If the urine output doesn’t respond to furosemide alone, the addition of a thiazide diuretic has been shown to achieve sufficient diuresis in some patients. However, if diuresis proves futile, RRT should be emergently arranged.10
2. Hyperkalemia. Along with hypervolemia, derangements in serum potassium are a common and serious complication of AKI. For patients with serum potassium levels of 5.0-5.4 mEq/L (i.e., mild hyperkalemia), medical management can be attempted to lower the extracellular potassium levels. However, medical management should only be attempted if the known cause of the AKI is established and easily reversible (i.e., true hypovolemia).
In patients with potassium values greater than 5.4 mEq/L, intractable/progressively worsening AKI, or conditions causing cell breakdown (i.e., rhabdomyolysis), emergent RRT must be arranged. An attempt at medical management can be done as a bridge to RRT, but dialyzing these patients is the primary goal.10
3. Metabolic acidosis. Acid/base balance within the kidneys is achieved by two mechanisms: 1) excretion of hydrogen ions; and 2) production of bicarbonate. When a patient is suffering from AKI, both mechanisms are impaired and metabolic acidosis ensues.
However, the metabolic acidosis that occurs because of AKI is a product of the buildup from the body’s daily metabolic processes. It’s important to remember that patients suffering from AKI are usually critically ill from other disease processes that greatly exacerbate the hydrogen ion burden of normal metabolism (e.g., lactic acidosis from sepsis, ketoacidosis from hyperglycemic crisis, etc.).
Like hyperkalemia, the treatments for AKI-induced metabolic acidosis are medical management or RRT. Any patient with scant urine production and severe acidosis (pH < 7.1) should be considered for emergent RRT. In severely acidotic states, the body’s normal physiology is extremely altered.
For instance, moderate to severe acidosis can lead to ventricular systolic dysfunction, lowered threshold for cardiac automaticity/ arrhythmia, arterial dilation, venous constriction, impairment of antibiotic efficacy and decreased responsiveness to adrenergic antihypertensives.
For patients with moderate to severe acidosis who aren’t hypervolemic, IV bicarbonate can be administered with caution. Bicarbonate administration can come with some serious risks and should only be administered with expert consultation. Bicarbonate administration in patients who are already volume overloaded should be avoided with the plan to seek emergent RRT.
Due to the large sodium burden of IV bicarbonate, a patient’s hypervolemia can be exacerbated; even euvolemic patients can become volume overloaded from bicarbonate, especially when oliguric. Patients with worsening acidosis and oliguria from an AKI that’s unlikely to be quickly reversed, should be referred for emergent RRT. This is especially true in cases where the pH is expected to progress to < 7.1.
4. Uremia. The clearance of metabolic waste is the primary function of the kidneys. When these waste products build up within the body as a result of AKI, they can become toxic and interfere with a host of normal physiologic processes.
The most common results of high uremic toxin burden are uremic encephalopathy, neuropathy, pericarditis and uremic bleeding. Collectively, these conditions are known as uremia or uremic syndrome.
Although the physiologic processes for most of these complications aren’t fully understood, it’s well accepted that all are direct results of the increased load of these toxins within the body. In uremic encephalopathy, the toxins interfere with the actions of neurotransmitters.
For neuropathies, the toxins can degrade myelin. These toxins also impede the actions of both platelets and the clotting factors needed for hemostasis.
The mechanism that leads to inflammation of the pericardial sack is poorly understood, though there appears to be a relationship to severe azotemia and the development of pericarditis. Regardless of the clinical manifestation, the only treatment for uremic syndrome is RRT.10
RRT & Dialysis
The process by which metabolic waste products are artificially removed from circulation has been traditionally known as “dialysis.” However, this may be a bit of a misnomer, as hemodialysis is one of the specific modalities of RRT-a more accurate term to describe the artificial process for removing waste products from the body.
Traditional outpatient RRT that prehospital providers are familiar with is highly efficient so that patients need only spend a few hours in treatment per week. However, this efficiency comes with a cost. It’s quite taxing on the body, leading to significant complications in critically ill patients.
This efficiency requires a large extracorporeal circuit and typically removes several liters of fluid volume per treatment session. In addition to the actual volume removed from the body during the treatment, there’s a second fluid shift that occurs from solute removal. As molecules are filtered out of the blood, there’s an abrupt fall in plasma osmolality. The sudden decrease in solutes causes an osmotic propulsion of free water into the body’s cells. Simultaneously these phenomena can lead to an aggressive change in fluid status that’s not well-tolerated and can be fatal in critically ill patients. One of the most frequent complications of RRT is hypotension. Any episode of hypotension in patients with AKI can further insult the already weakened kidneys.
For these reasons, an alternative form of RRT was developed several decades ago. Continuous renal replacement therapy (CRRT) is like RRT in terms of its actual function; however, the main difference is that CRRT is performed continuously over a period of days. Certain centers may elect to vary the treatment schedule so that each treatment last 12-16 hours a day for several days instead of 24 hours a day. However, for the purpose of this article, we’ll use CCRT to collectively refer to all of the slow modalities of RRT. (See Figure 1.)
Figure 1: Modalities for administration of continuous renal replacement therapy (CRRT)
There’s also a growing body of evidence supporting the use of hemofiltration in critically ill sepsis patients with concomitant AKI. Since hemofiltration is better at moving medium- and large-sized molecules, it’s hypothesized that hemofiltration during CRRT may remove many of the inflammatory mediators that perpetuate the septic pathway. Removal of these substances may not only help reverse the AKI, but may also help preserve the cardiovascular function that can be impaired by their high serum concentration.11
Critically ill patients who develop an AKI are some of the most challenging and resource- intensive patients in the ICU. They often require care from a host of specialties, advanced medical technology and a large amount of human resources. Providing care for these patients is extremely complex.
Early in my training, I had a professor who was a retired internist. She had a catchphrase that’s served me well over the years: “When the kidneys aren’t working correctly, nothing else is either.” Providers called to care for these patients must exercise robust critical thinking, prudent decision-making and sound clinical judgment.
When preparing to care and transport these patients, a report detailing the transfer of care and history of present illness is needed. In that report, there are several things that you’ll want to pay close attention to:
>>Volume status. In most cases, these patients will be hypervolemic. You’ll want to know by how much. This is tracked in the medical record as ins and outs (i.e., I/O, or “Is and Os”). It’s conveyed in liters and balanced against volume loss from urine output, blood loss, etc. You’ll typically hear it reported as “the patient is 4.5 L positive.” Any patient presumably symptomatic from volume overload should be administered fluid only when absolutely necessary.
>>Baseline electrolytes and arterial blood gas. Although there’s no evidence that clearly lays out any type of a schedule for how often a patient’s electrolytes should be monitored while suffering from an AKI,10 I’m very cautious with an AKI patient who has any known electrolyte derangements or issues with hemodynamic stability. Pay close attention to electrolytes and blood gasses if there have been any treatments to correct an imbalance, such as the administration of calcium, bicarbonate, hypertonic saline, etc. For the purposes of transport, a complete metabolic panel and an arterial blood gas should be no less than eight hours old. If there’s been any gross changes in hemodynamics, those test results should be no more than four hours old-especially if the transport time is more than an hour.
>> Trends in pulmonary/cardiovascular status. Patients with a critical illness that’s superimposed by an AKI can have a very tenuous course.Their hemodynamic status can swing wildly from one hour to the next. It’s imperative to know how the patient’s heart and lungs have been responding to the illness at hand. This information will help you be prepared for the future. If you’re told that a patient’s SpO2 was 100% eight hours ago, and it’s now 90% on 100% oxygen, there’s a very high likelihood that this patient may continue to have problems with oxygenation. The same is true of blood pressure and heart rate.
>> Previous treatments and response. The way a patient responded to therapies previously will help you as you begin to formulate your treatment plan. It’s important to know whether dialysis was sattempted. For instance, it’s not uncommon to hear that a patient is being transferred for CRRT. It’s important to note that the referring facility tried traditional RRT twice already, but the patient became too hemodynamically unstable several hours into or after the treatment. This is likely due to the delayed fluid shift that happens from the removal of solutes. Don’t let these little details slip past you; they’re especially important if the last RRT attempt was several hours prior to your arrival.
Monitoring these patients during transport is fairly straightforward. However, providers must pay close attention to trends in heart rate, respiration, blood pressure and oxygenation status. Any trends that suggest hemodynamic instability need to be immediately appreciated, and a plan for how to correct for these issues should be formulated.
When confronted with the complexity and frailty of these patients, most providers will quickly realize the limits of their expertise. Our physician colleagues should be contacted early and often in these instances. Obtaining medical direction to help guide your therapies shouldn’t be a last resort. Effective collaboration can mean life or death for these patients.
AKI poses a substantial risk to critically ill patients. The impact on mortality and morbidity is great, as is the resource-intense nature of the illness. As healthcare begins to become more efficient, EMS providers need to be adequately prepared to safely and expertly transport these critically ill patients to the tertiary and quaternary care facilities they need.
Learn more from Robert Girardeau at EMS Today: The JEMS Conference & Exposition, February 21-23, in Charlotte, N.C. Visit EMSToday.com for additional information.
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9. Girardeau R. From beginning to endotracheal: How to anticipate & treat the most common complications of prehospital intubation. JEMS. 2016;41(10):58-63.
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