Bongard Frederic , Darryl Sue. Diagnosis and Treatment Critical Care

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B. Laboratory Findings—In the absence of detectable red

blood cells in the urine, a urinalysis dipstick positive for

heme is virtually diagnostic of hemoglobinuria or myoglo-

binuria. Similarly, a highly positive heme reaction (3+ or 4+)

in the face of minimal hematuria (3–5 red cells/high-power

field [hpf]) is equally suspicious. Since myoglobin is suffi-

ciently small to be filtered, patients with myoglobinuria have

brown urine, but the serum is clear. In contrast, hemoglobin-

uria also may produce a dark brown urine, but the spun

serum sample is pink because haptoglobin-bound hemoglo-

bin is a complex that is too large to be filtered. Further con-

firmation of the diagnosis is seen in serum chemistry values.

Rhabdomyolysis is associated with elevated creatine kinase

(CK) and other muscle-derived enzymes released into the

circulation, including aspartate aminotransferase (AST), lac-

tate dehydrogenase (LDH), and aldolase. Of these, aldolase is

specific for muscle damage. Occasionally, creatinine released

from damaged muscle leads to an abnormally low BUN:cre-

atinine ratio (<10:1). Severe hemolysis capable of producing

renal failure is usually associated with detectable free hemo-

globin levels above 25 mg/dL and a marked decrease in free

haptoglobin. As with rhabdomyolysis, elevated LDH and

AST may be present; thus these abnormalities do not permit

distinction between the two disorders.

C. Imaging Studies—Imaging studies are not helpful in

diagnosis of pigment nephropathy other than in evaluating

the extent of injury in patients with traumatic rhabdomyol-

ysis. In patients with serious trauma with renal failure, how-

ever, injury to the kidneys, ureters, bladder, or urethra should

be considered, and ultrasound, CT scan, or IVP may be help-

ful in distinguishing direct injury from rhabdomyolysis.

Treatment

The single most important therapeutic maneuver is to

restore circulating volume rapidly and initiate diuresis. If

oliguria is present, a single dose of mannitol, 12.5 g intra-

venously, can be given to promote diuresis. If successful,

mannitol can be continued as a 5% infusion. Alternatively,

furosemide, 40–200 mg intravenously, can be given and

repeated every 6 hours if necessary. Forced diuresis with

aggressive hydration should strive for a urine output of at

least 100 mL/h and should be maintained until levels of cre-

atine kinase or haptoglobin begin to normalize.

Alkalinization of the urine is recommended by some, but

there is no definitive evidence that it is necessary.

Rhabdomyolysis is commonly associated with several

potentially troublesome electrolyte disorders. Hypocalcemia

may be seen early, probably as a consequence of precipitation

of calcium salts owing to associated hyperphosphatemia.

Despite extremely low levels of serum calcium, tetany is

uncommon, perhaps owing to the associated acidosis. Severe

hyperuricemia also may be encountered. Hyperkalemia,

sometimes extremely difficult to control, may be encoun-

tered with both rhabdomyolysis and hemolysis. In contrast,

crush victims who have received early and vigorous fluid

resuscitation and who present with polyuria may develop

hypokalemia. Hypercalcemia during the recovery phase may

be the result of calcium release from healing muscle and an

increase in 1-25 dihydroxyvitamin D.

Better OS, Stein JH: Early management of shock and prophylaxis

of acute renal failure in traumatic rhabdomyolysis. N Engl J

Med 1990;322:825–9. [PMID: 2407958]

Gunal AI et al: Early and vigorous fluid resuscitation prevents

acute renal failure in the crush victims of catastrophic earth-

quakes. J Am Soc Nephrol 2004;15:1862–7. [PMID: 15213274]

Malinoski DJ, Slater MS, Mullins RJ: Crush injury and rhabdomy-

olysis. Crit Care Clin 2004;20:171–92. [PMID: 14979336]

2. Pulmonary Renal Syndromes

Any type of acute renal failure can present with fluid over-

load and pulmonary edema, but there are several conditions

in which simultaneous involvement of both lung and kidneys

is a common presentation or an intrinsic part of the basic

pathogenesis (Table 13–8). Of these, two are of particular

importance because their rapid identification and subse-

quent treatment can be lifesaving: Goodpasture’s syndrome

and paraquat intoxication.

Goodpasture’s Syndrome

Goodpasture’s syndrome is an autoimmune disease charac-

terized by the formation of anti-GBM antibodies that attack

Disease Renal Involvement

Goodpasture’s syndrome RPGN

Wegener’s granulomatosis RPGN

Systemic lupus erythematosus RPGN

Churg-Strauss syndrome RPGN

Sarcoidosis Interstitial nephritis

Scleroderma Hypertensive renal crisis

Pulmonary embolism Prerenal azotemia

Pneumonia Prerenal azotemia

Poisons (paraquat) Actue tubular necrosis

Congestive heart failure Prerenal azotemia

Adult respiratory distress

syndrome

Acute tubular necrosis, prerenal

azotemia

Key: RPGN = rapidly progressive glomerulonephritis; ATN = acute

tubular necrosis

Table 13–8. Pulmonary-renal syndromes causing acute

renal failure.

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both the pulmonary capillary and the glomerulus. The clas-

sic clinical presentation is that of a young male smoker with

signs of acute glomerulonephritis (ie, hematuria, protein-

uria, and red blood cell casts) and hemoptysis associated

with bilateral pulmonary infiltrates. Iron deficiency anemia

is also a frequent finding.

The diagnosis of Goodpasture’s syndrome can be made

by detecting serum levels of anti-GBM antibodies or by lin-

ear immunofluorescence of the GBM on renal biopsy.

Unfortunately, availability of these confirmatory tests may be

delayed, and rapid initiation of treatment often depends on a

high degree of suspicion. Early initiation of treatment is

essential because therapeutic success in reversing renal fail-

ure is rare if the therapy is started after the onset of oliguria.

Aside from smoking, genetic predisposition and hydrocar-

bon exposure have been identified as associated risk factors.

Both life-threatening hemoptysis and rapidly progressive

renal failure can be treated successfully with a combination

of corticosteroids, cyclophosphamide, and 2 weeks of daily

plasma exchange.

Pusey CD: Anti-glomerular basement membrane disease. Kidney

Int 2003;64:1535–50. [PMID: 12969182]

Pusey CD: The continuing challenge of anti-neutrophil cytoplasm

antibody-associated systemic vasculitis and glomerulonephritis.

J Am Soc Nephrol 2006;17:1221–3. [PMID: 16624927]

Paraquat Poisoning

Paraquat is a herbicide used in concentrated solutions.

Ingestion is highly corrosive for the oral and esophageal

mucosa, and net absorption results in pulmonary edema and

anuria. Effective treatment involves gastric lavage and aggres-

sive use of charcoal adsorbents. Daily treatments with char-

coal hemoperfusion or high-efficiency hemodialysis may be

helpful in lowering paraquat levels. There is also reason to

believe that low oxygen tension may limit lung injury.

Consultation with a poison control expert should be sought.

Web site information can be obtained from the national pes-

ticide information network at http://ace.orst.edu/info/nptn/

Van Vleet TR, Schnellmann RG: Toxic nephropathy: Environmental

chemicals. Semin Nephrol 2003;23:500–8. [PMID: 13680539]

3. Hepatorenal Syndrome

Conditions associated with combined hepatic and renal fail-

ure include infections (eg, sepsis, hepatitis, and leptospiro-

sis), drug toxicity (eg, acetaminophen, allopurinol, rifampin,

and methoxyflurane), poisons (eg, rodenticide and carbon

tetrachloride), and autoimmune disorders (eg, systemic

lupus erythematosus, vasculitis, and cryoglobulinemia).

More common, however, is prerenal azotemia associated

with cirrhosis. Patients presenting with this combination

often have signs of advanced liver disease, hypoalbuminemia,

and ascites. Under these conditions, if prerenal azotemia

becomes unresponsive to intravascular volume replacement,

a diagnosis of hepatorenal syndrome becomes appropriate.

This syndrome is a condition of severe renal vasoconstriction

presenting with extremely low urinary sodium (<10 meq/L),

decreased FE

urea

(<20%), an extremely high urine:plasma

creatinine ratio, and a relatively unimpressive urine sediment

showing bile-pigmented casts.

Until recently, hepatorenal syndrome was considered to

be almost universally fatal, rendering preventive measures as

the most important management option. Most patients with

hepatorenal syndrome develop the problem during hospital-

ization. GI hemorrhage, bacterial peritonitis, and the

overzealous use of diuretics to control ascites all have been

shown to be associated with the precipitation of the hepa-

torenal syndrome. Thus it is crucial that all patients present-

ing with liver disease and prerenal azotemia receive

aggressive volume repletion. In many cases, pulmonary

edema and ascites may be limiting factors in repletion; cen-

tral venous pressure or pulmonary artery catheterization

may be required to adequately judge how much fluid can be

administered safely. With increasing central venous pressure,

there also will be the increased risk of variceal hemorrhage.

In patients with peripheral edema associated with hypoalbu-

minemia, albumin infusions can successfully mobilize fluid

into the intravascular space, but ascites formation increases

in approximately one-third of patients. In the same vein,

high-volume paracentesis should be performed in conjunc-

tion with intravenous albumin infusions to minimize the

tendency for intravascular volume depletion.

Successful reversal of well-established hepatorenal syn-

drome is rare, but several new treatment strategies appear to

offer some success. The combined use of midodrine (an α

adrenergic agonist) and octreotide (a somatostatin analogue)

may improve renal hemodynamics and subsequent survival.

The use of vasopressin analogues in conjunction with albu-

min infusions also may improve renal perfusion, but there is

also the risk of ischemia. Interestingly, since the hepatorenal

syndrome is a result of a severe renal vasoconstriction, the

renal parenchyma may remain intact, and liver transplanta-

tion has been associated with return of renal function.

Recently, there have been reports in Europe of successful

treatment of hepatorenal syndrome with albumin-based

dialysis (molecular adsorbent recycling system [MARS]).

Cardenas A, Gines P: Hepatorenal syndrome. Clin Liver Dis

2006;10:371–85. [PMID: 16971267]

Gluud LL et al: Terlipressin for hepatorenal syndrome. Cochrane

Database Syst Rev 2006;4:CD005162. [PMID: 17054242].

Mitzner SR et al: Improvement of hepatorenal syndrome with

extracorporeal albumin dialysis MARS: Results of a prospective,

randomized, controlled clinical trial. Liver Transplant

2000;6:277–86. [PMID: 10827226]

Moreau R, Lebrec D: The use of vasoconstrictors in patients with

cirrhosis: Type 1 HRS and beyond. Hepatology 2006;3:385–94.

[PMID: 16496352]

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Moreau R, Lebrec D: Diagnosis and treatment of acute renal fail-

ure in patients with cirrhosis. Best Pract Res Clin Gastroenterol

2007;21:111–23. [PMID: 17223500]

Wong F, Pantea L, Sniderman K: Midodrine, octreotide, albumin,

and TIPS in selected patients with cirrhosis and type 1 hepatore-

nal syndrome. Hepatology 2004;40:55–64. [PMID: 15239086]

4. Renal Failure in AIDS

Acute renal failure occurs in more than 50% of hospitalized

patients with AIDS. The combination of volume depletion,

nephrotoxic medications, and sepsis accounts for most cases

(Table 13–9), but most AIDS patients presenting with acute

renal failure can recover renal function and be discharged

from the hospital.

Intravascular volume depletion can result from poor fluid

intake, fever, and GI disturbances or may be secondary to

hypoalbuminemia owing to nephrotic syndrome or malnutri-

tion. Enlarged periaortic lymph nodes can obstruct lower

extremity venous return, resulting in severe leg edema but

insufficient central venous pressure. Careful attention to

restoring intravascular volume not only reverses prerenal

azotemia but also will serve to reduce substantially the risk of

nephrotoxicity associated with medications and radiocontrast

agents. In many cases of drug-induced renal failure, renal

function may return rapidly after termination of exposure to

the drug, such as can be seen with NSAIDs and the crystalluria

associated with indinavir and acyclovir. In other cases, a full-

blown syndrome of acute tubular necrosis may develop; this

disorder may require dialytic therapy before recovery.

A renal syndrome that seems to be unique to

patients with AIDS is rapidly progressive focal segmental

glomerulosclerosis. This syndrome is most common in

patients of African descent and is associated with nephrotic-

range proteinuria (>3 g/day), enlarged, hyperechogenic kid-

neys on renal ultrasound, and—in contrast to focal

segmental glomerulosclerosis in the non-AIDS population—

normotension. Progression of this type of renal disease can

be explosive, reaching a stage of irreversible renal failure in

weeks or months. Recent experience, however, suggests that

the new highly active antiretroviral therapy (HAART) regi-

mens can slow the progression of this type of AIDS

nephropathy.

Standard precautions during hemodialysis are employed

to limit transmission of HIV and hepatitis B. In addition,

HIV has been identified in peritoneal dialysate from patients

with AIDS, and this effluent should be handled with appro-

priate precautions.

Hyun G, Lowe FC:. AIDS and the urologist. Urol Clin North Am

2003:30;101–9. [PMID: 12580562]

Khan S, Haraqsim L, Laszik ZG et al: HIV-associated nephropathy.

Adv Chron Kidney Dis 2006;13:307–13. [PMID: 16815235]

Kimmel PL, Barisoni L, Kopp JB: Pathogenesis and treatment of

HIV-associated renal diseases: Lessons from clinical and animal

studies, molecular pathologic correlations, and genetic investi-

gations. Ann Intern Med 2003;139:214–26. [PMID: 12899589]

Wyatt CM, Klotman PE: HIV-associated nephropathy in the era of

antiretroviral therapy. Am J Med 2007;120:488–92. [PMID:

17524746]

5. Renal Failure in the Renal Transplant

Recipient

Acute renal failure in the transplant recipient can be arbitrar-

ily defined as being early (<10 days after transplantation) or

late (>10 days). In the early period, acute renal failure may be

due to ischemic acute tubular necrosis of the transplanted

graft, acute or hyperacute immunologic rejection, or techni-

cal problems related to the surgery (eg, obstruction, leak, or

infection of the renal artery or vein or of the ureter). Acute

drug toxicity from cyclosporine can present as prerenal

azotemia associated with hypertension and is encountered

most often with relatively elevated intravenous dosing.

Acute renal failure in the late period may be the result of

acute rejection, cyclosporine toxicity, ureteral obstruction,

renal artery stenosis, or recurrence of the original renal dis-

ease. Acute rejection may present with fever, graft tenderness,

and swelling where the kidney is implanted into the iliac

fossa, but concurrent immunosuppressive therapy with

steroids or cyclosporine may mask these signs. If the history,

physical examination, and imaging studies (ie, ultrasound

and nuclear flow scans) cannot distinguish the cause of renal

failure, renal biopsy may be required. In any event, prompt

and continued consultations with the patient’s transplant sur-

geon and nephrologist are essential to proper management.

The intensivist is often in a position to identify potential

organ donors. Acceptable donors for renal transplantation

Table 13–9. Causes of acute renal failure associated with

AIDS.

Prerenal azotemia

Volume depletion, hypoalbuminemia, NSAIDs

Acute tubular necrosis

Pentamidine, amphotericin B, aminoglycosides, foscarnet, acyclovir,

radiocontrast agents, sepsis, shock

Allergic interstitial nephritis

Trimethoprim-sulfamethoxazole, phenytoin

Rapidly progressive focal segmental glomerulosclerosis

Obstructive uropathy

Sulfadiazine-related crystalluria, lymphoma, retroperitoneal fibrosis

Nephrolithiasis

Indinavir-induced crystalluria

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

Renal edema

Hypoalbuminemia with massive proteinuria

Multiple myeloma

Acute glomerulonephritis

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330

are aged 6 months to 60 years with no identifiable renal dis-

ease, no active infection, and no malignancy (except brain

tumors). Physicians working in the ICU should familiarize

themselves with local laws and policies regarding the pro-

curement of organs and the criteria for brain death.

Kasiske BL et al: Recommendations for the outpatient surveillance

of renal transplant recipients. American Society of

Transplantation. J Am Soc Nephrol 2000;11:S1–86. [PMID:

11044969]

Silkensen JR: Long-term complications in renal transplantation. J

Am Soc Nephrol 2000;11:582–8. [PMID: 10703683]

Venkat KK, Venkat A: Care of the renal transplant recipient in the

emergency department. Ann Emerg Med 2004;44:330–41.

[PMID: 15459617].

NONDIALYTIC THERAPY FOR ACUTE RENAL

FAILURE



Fluid Balance

Achieving the appropriate fluid balance in the setting of an

ICU involves two potentially conflicting goals: providing suf-

ficient volume to ensure adequate renal perfusion and avoid-

ing volume overload with resulting pulmonary congestion.

In some patients, when decreased renal perfusion is sus-

pected in the context of pulmonary compromise, only a pul-

monary artery catheter will yield sufficient information to

guide appropriate therapy. Optimal fluid management for

acute renal failure can be divided arbitrarily into three peri-

ods: (1) the prevention phase, during the initial onset of olig-

uria, (2) the oliguric phase, once renal failure is well

established, and (3) the recuperative phase, often heralded by

relative polyuria. Not all episodes of acute renal failure pass

through each of these phases, but a discussion of their man-

agement is a useful guide to overall treatment goals.

Prevention Phase

On initial presentation, the onset of oliguria should call for

prompt evaluation of the type of renal dysfunction. If vol-

ume depletion is suspected, rapid restoration of circulating

volume may prevent ischemic damage. Restoration of ade-

quate circulating volume can be achieved by administration

of crystalloid or colloid. If simple fluid repletion is required,

normal saline usually suffices. In the context of hypoalbu-

minemia and edema, intravenous albumin can serve to draw

excess extravascular fluid into the circulation.

If oliguria persists despite adequate fluid replacement and

acute tubular necrosis is suspected, a short trial of diuretic

therapy may offer some benefit in limiting renal damage. A

single intravenous 12.5-g dose of mannitol may initiate

diuresis and has the theoretical advantage of limiting epithe-

lial cell swelling and intratubular precipitation of cellular

debris. If initially unsuccessful, further mannitol administra-

tion is potentially harmful in that it may lead to poorly

tolerated intravascular expansion. Alternatively, furosemide

may be given intravenously at a dose of 200 mg (1-hour infu-

sions are preferable to more rapid injection) and may be

repeated safely within 6 hours. Dosages above 1 g/day have

been associated with ototoxicity. If, despite the preceding

maneuvers, oliguria persists more than 24 hours, diuretics

should be discontinued, and the physician should be pre-

pared to manage a potentially prolonged period of oliguria.

Oliguric Phase

The oliguric phase of acute renal failure may persist for sev-

eral weeks. During this period, especially in the critical care

setting, the patient may require enormous amounts of intra-

venous fluids, including hyperalimentation, vasopressors,

and antibiotics. Every effort should be made to minimize the

volume of these infusions. Continuous infusions of vaso-

pressors should be maximally concentrated, and antibiotics

should be given in minimum volumes of fluid. When given

in adequate amounts, parenteral hyperalimentation always

requires 1–2 L/day. Thus enteral alimentation is always pre-

ferred when possible.

Proper maintenance of fluid balance requires careful

attention to all avenues of fluid intake and output, including

surgical drains, nasogastric suction, and diarrhea. Normal

insensible losses can equal 1000 mL/day but can increase

substantially in the presence of fever, burns, or exfoliative

dermatitis. Increased minute ventilation enhances water loss

from the lungs even if the inspired gas is humidified. On the

other hand, metabolism of carbohydrate and fat yields

approximately 500 mL/day of metabolically produced water.

Thus, unless insensible losses are increased, an anuric patient

requires only 500 mL/day of water. Finally, despite meticu-

lous monitoring of fluid input and output, there can be no

substitute for daily weight measurements.

Recuperative Phase

In many patients with acute renal failure, the oliguric phase

is followed by a period of relative polyuria, heralding the

beginning of tubular recuperation. During this period,

serum urea nitrogen and creatinine may remain elevated,

and renal dysfunction persists. One must bear in mind that

the urine produced is not appropriately concentrated and

that reabsorption of sodium and other ions is inadequate.

During this phase, it is the goal of management to replace

lost volume and electrolytes. Urinary sodium and potassium

should be measured and replaced in appropriate amounts.

Abnormalities of magnesium, calcium, and phosphate also

should be anticipated.

Monitoring Fluid Balance

In the presence of active pulmonary disease such as pneumo-

nia, acute respiratory distress syndrome (ARDS), or pul-

monary edema and suspected prerenal azotemia, aggressive

fluid replacement may worsen pulmonary gas exchange.

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331

Furthermore, in patients with vasodilatory shock or hypoal-

buminemia, substantial edema may be present, and still the

patient has insufficient circulating volume. In these settings,

intravascular pressure monitoring becomes invaluable.

Although central venous pressure can be monitored easily

via subclavian, internal jugular, or femoral vein catheteriza-

tion, a more definitive assessment of optimal cardiac filling

pressures can be obtained with pulmonary artery catheteri-

zation. This is because central venous pressure can be

increased by pulmonary hypertension or central venous

thrombosis or occlusion even in a volume-depleted patient.

Similarly, positive-pressure ventilation and, especially, posi-

tive end-expiratory pressure may elevate pulmonary capil-

lary wedge pressure spuriously.



Acid-Base Balance

Uremic acidosis occurs as a result of the slow accumulation

of phosphates and sulfates and is related to protein catabo-

lism. Approximately 1 meq acid is retained for every gram of

protein catabolism. Thus a 70-g protein diet yields approxi-

mately 70 meq acid, which, when distributed into the total

body water compartment, consumes approximately 2 meq

bicarbonate per liter per day. Replacement of this amount of

bicarbonate is relatively easy and can be in the form of intra-

venous sodium bicarbonate, orally administered sodium or

potassium citrate, or as acetate in hyperalimentation solu-

tion (1 meq acetate converts to 1 meq bicarbonate plus some

energy). The patient’s tolerance for the associated sodium

and potassium load should be considered.

Patients with prolonged uremia may present with a sub-

stantial buffer deficit (serum bicarbonate <15 meq/L),

Kussmaul respirations, and associated hypocalcemia. In this

situation, bicarbonate replacement relieves the dyspnea by

correction of acidosis, but the rapid increase in serum pH

may precipitate tetany. Under these conditions, after deter-

mination of serum calcium and phosphate, it may be pru-

dent to administer 1 ampule of calcium gluconate after the

first 50–100 meq of bicarbonate. However, if phosphate lev-

els are particularly elevated, there is a theoretical risk of

metastatic calcifications with calcium administration.

Lactic acidosis is potentially a more difficult problem. In

the presence of insufficient tissue oxygenation, lactic acid

production can exceed 50 meq/h. This amount of acid low-

ers serum bicarbonate at a rate of 1–2 meq/L per hour. In the

face of oliguria, replacement of this amount of bicarbonate

would risk intravascular fluid overload and hypernatremia

and may require dialytic therapy. Therefore, in lactic acido-

sis, an aggressive effort to restore adequate tissue perfusion is

the mainstay of treatment.

Metabolic alkalosis is an uncommon complication of

acute renal failure, but it may occur as a result of massive

losses from gastric suctioning. Decreasing net acid loss can

be achieved by raising gastric pH with H

blockers such as

cimetidine or ranitidine or with proton pump inhibitors

such as omeprazole or lansoprazole. If these efforts fail, acid

can be given carefully as arginine hydrochloride or dilute

hydrochloric acid. These treatments can produce severe life-

threatening hyperkalemia and must be given with vigilant

monitoring of potassium levels.



Electrolytes

Sodium

Sodium balance in acute renal failure is maintained by eval-

uation and matching of sodium losses. Urinary losses are

best measured with 24-hour collections but can be reason-

ably assessed by random sampling and multiplication of

sodium concentration by the day’s total urine volume. After

diuretic administration, urinary sodium will be increased for

several hours and may not reflect a constant excretion rate.

GI losses must be either measured (eg, nasogastric suction)

or estimated (eg, diarrhea)(Table 13–10).

In oliguric renal failure, hyponatremia is the most com-

mon electrolyte abnormality and is almost always the result

of excessive free water administration. Since most fluid losses

are lower in sodium when compared with serum (see Table

13–10), a reasonable initial approach is to add 50 meq

sodium to each liter of infused fluid, most notably the hyper-

alimentation fluid. Daily monitoring of serum sodium

allows for readjustment of water and sodium administered as

necessary.

Potassium

Hyperkalemia is the most serious electrolyte abnormality

associated with acute renal failure. Cardiotoxicity, however,

does not correlate strictly with the measured serum potas-

sium and may be encouraged by acidosis, serum calcium

concentration, and medications. The most rapid and reliable

means for assessing cardiotoxicity is to obtain an ECG, which

may show hyperkalemia in the form of peaked T waves, a

prolonged PR interval, diminished to absent P waves, widen-

ing of the QRS complex, prolongation of the QT interval,

Sodium Content of Intravenous Sodium Content of

Infusion Fluids Body Fluids

1 g Na

= 43 meq Na

Gastric fluid = 30–90 meq

1 g NaCl = 17 meq Na

Na+ per liter

1 L of 0.9% NaCl = Diarrhea = 50–110 meq

154 meq Na

Na+ per liter

1 L of 0.45% NaCl = Small bowel ostomy = 70–150

77 meq Na

meq Na

per liter

1 L of Ringer’s lactate = Biliary drainage = 120–170 meq

130 meq Na

per liter

50 mL of 7.5% NaHCO

= Sweat = 20–100 meq Na

per liter

44 meq Na

Table 13–10. Sodium content: intake and output.



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332

and ultimately, a sine wave pattern. Immediate management

requires medications designed to stabilize the myocardial

membrane and promote intracellular movement of potas-

sium. Infusion of calcium, bicarbonate, and insulin with glu-

cose temporarily improves the electrocardiographic

abnormalities. Definitive procedures for removing potas-

sium should be initiated as soon as possible.

In oliguric patients unresponsive to diuretic therapy,

exchange resins of sodium polystyrene sulfonate are the most

efficient means of extracorporeal potassium removal.

Administration can be either orally or by retention enema

for at least 30 minutes (orally: 50 g resin in 150 mL 20% sor-

bitol; by enema: 50 g resin in 200 mL tap water to avoid

sorbitol-induced colonic irritation). These doses can be

repeated every hour as necessary. Each potassium ion

removed will be exchanged for a sodium ion—a situation

that may be poorly tolerated in the hypernatremic or fluid-

overloaded patient. In addition, to avoid the possibility of

forming intraluminal concretions, sodium polystyrene sul-

fonate never should be given concurrently with aluminum

hydroxide (used as a phosphate binder or antacid). When

these measures are poorly tolerated because of fluid overload

or hypernatremia—or when the GI tract is not available for

use—dialytic therapy should be considered.

Maintaining potassium balance requires evaluation of

renal and extrarenal losses (Table 13–11). A normal diet con-

tains approximately 70–100 meq potassium per day, and

dietary potassium restriction to 2 g (50 meq) per day is rea-

sonable for patients with oliguric renal failure.

Calcium

Hypocalcemia often accompanies chronic renal failure and is

the result of hyperphosphatemia and altered vitamin D

metabolism. In acute renal failure, hypocalcemia may be

associated with the hyperphosphatemic phase of rhabdomy-

olysis or may occur during administration of the antiviral

agent foscarnet. Hypercalcemia is seen in multiple myeloma

or hyperparathyroidism. Urinary calcium losses are minimal

during acute renal failure. Frank tetany is rare and is usually

the result of overly aggressive correction of acidosis. Since

hypoalbuminemia and acid-base disturbances are common

in the critically ill patient, ionized calcium levels, when avail-

able, are preferred to total serum calcium.

Magnesium

Magnesium excretion is limited during renal failure, and

magnesium-containing antacids such as Maalox and

Mylanta should be avoided. Magnesium wasting may

occur with amphotericin- or cisplatin-induced renal fail-

ure or during the polyuric recuperative phase of acute

tubular necrosis.

Phosphate

Hyperphosphatemia results from insufficient renal excretion

and secondary hyperparathyroidism. Avoiding hyperphos-

phatemia limits the risk of metastatic calcifications and helps

to maintain normal levels of ionized calcium. Diets should

be limited to 800 mg/day of phosphorus, but even at this

level, oral phosphate binders are required to limit GI absorp-

tion. When serum phosphorus exceeds 6 mg/dL, aluminum

hydroxide antacid can be given at a dosage of 30 mL with

each meal and at night. Sevelamer at a dose of 800–1600 mg

with each meal also can be used as an effective phosphate

binder and has the advantage of not presenting the potential

for aluminum toxicity or the constipation associated with

aluminum hydroxide.

When levels are controlled below 6 mg/dL, calcium car-

bonate at 500 mg with each meal or calcium acetate at 667

mg with each meal can be initiated. Intravenous hyperali-

mentation should be prepared without phosphate until levels

are normalized. However, once normal phosphorus levels are

reached, intravenous hyperalimentation solutions should

contain approximately 100–250 mg phosphorus per day

(5–10 meq sodium or potassium phosphate). In the presence

of renal failure, hypophosphatemia is almost always the result

of prolonged parenteral nutrition devoid of phosphate.



Nutrition

Nitrogen Balance

Several studies have suggested that appropriate nutritional

support can promote renal recovery and improve overall

survival in patients with acute renal failure. Unfortunately,

there is often conflict between giving adequate protein

replacement while at the same time limiting the production

of nitrogenous wastes. Under ideal conditions, an adequate

diet should include 1 g/kg per day of protein and 35–40

kcal/kg per day of carbohydrates and fats. There is no defin-

itive evidence that diets with substantially more than 1.2 g/kg

per day of protein enhance survival rates or reduce morbidity,

Table 13–11. Potassium content: intake and output.

Intake

2 g K

in diet = 50 meq

Output

Gastric fluid = 4–12 meq K

Abdominal drainage = approximately the serum level

Diarrhea = 10–30 meq K

Sorbitol-induced diarrhea = 30–40 meq K

Sodium polystyrene sulfonate (Kayexalate) = 1 meq K

/g of retained

absorbent per hour

Urine = 5–150 meq K

Peritoneal dialysis (2 L/h), CAVH (1 L/h) = 5–10 meq K

∗

Hemodialysis = 40–60 meq K

∗

Assuming serum [K

] = 5 meq/L.

Key: CAVH = continuous arteriovenous hemofiltration



RENAL FAILURE

333

with the possible exception of the patient with extensive

burns. Overly aggressive protein feeding (>2 g/kg per day) is

unwarranted and can lead to abnormally high amino acid

levels and an unnecessary increase in retained nitrogen

wastes. In the very stable patient with minimal net negative

nitrogen balance (<5 g/day), protein intake can be limited to

0.6 g/kg per day. In the nonoliguric patient, this may reduce

the need for dialysis, but careful attention to nitrogen bal-

ance is required.

Nitrogen balance can be evaluated easily by measuring

the rate of urea production, commonly referred to as the urea

nitrogen appearance (UNA). The daily UNA can be measured

by obtaining a 24-hour urine for urea nitrogen measurement

and evaluating the change in BUN occurring at the begin-

ning and end of the 24-hour collection. The UNA then can

be calculated using the following formula:

where UNA equals the daily urea nitrogen appearance in

grams per day, BUN

and BUN

are the levels of blood urea

nitrogen in milligrams per deciliter at the beginning and end

of the 24-hour urine collection, total body water in liters is

estimated as 60% of lean body mass plus the amount of any

extra edema fluid, and UUN is the urine urea nitrogen

expressed as grams per day.

Under conditions of nitrogen balance, UNA depends on

protein ingestion and can be calculated as follows:

It is assumed that every 6.25 g of protein contains 1 g of

nitrogen and that the production of nonurea nitrogen is

30 mg/day per kilogram of lean body mass. The minimum

amount of urea clearance required to remove a given amount

of UNA can be calculated using the following formula:

When the preceding formulas are used, a 70-kg patient

receiving 1 g/kg per day of protein will receive 11 g nitrogen

(70 g ÷ 6.25). On balance, approximately 2 g nitrogen will

become nitrogenous wastes other than urea; the remaining

9 g will form urea.

On the other hand, many patients with acute renal failure

present with a degree of hypercatabolism. Under these con-

ditions, urea production is greatly enhanced owing to the

catabolism of endogenous proteins, and UNA can greatly

exceed that predicted from exogenous protein administra-

tion alone. For example, under conditions of severe stress,

endogenous protein breakdown can generate 30 g or more of

urea nitrogen per day, representing the catabolism of approx-

imately 200 g protein. In addition to enhanced proteolysis

accompanying hypercatabolism, increased urea production

is often the result of GI bleeding, with the ultimate break-

down and absorption of the blood and its proteins. There are

approximately 200 g protein per liter of whole blood.

Treatment of endogenous hypercatabolism and the nega-

tive nitrogen balance that results is controversial. Although

adequate nutrition is essential, it is often not sufficient to

match the ongoing catabolism. Several studies have demon-

strated that increased protein catabolism associated with

stress is mediated by hormones (eg, glucagon, cate-

cholamines, and cortisol) and cytokines (eg, interleukins,

tumor necrosis factor, etc.). For this reason, overly aggressive

protein administration is not only futile but yields unneces-

sary amounts of nitrogenous waste, thereby increasing the

need for dialysis therapy. Until specific therapy for cytokine

neutralization is available, the most successful strategy will

be to administer the majority of needed calories in the form

of carbohydrates, thus allowing for the maximum adminis-

tration of “anticatabolic” insulin.

Calories

Adequate caloric intake is essential to minimize negative

nitrogen balance and to improve overall survival. In the crit-

ically ill patient with acute renal failure, approximately

35 kcal/kg per day is a reasonable goal. Hyperglycemia

resulting from administration of large amounts of carbohydrate

can be managed with insulin.

Vitamins and Trace Elements

There is no evidence that patients with acute renal failure

have unique requirements for either vitamins or trace ele-

ments. Thus daily minimum requirements should be ade-

quate. Once dialysis is initiated, replacement of water-soluble

vitamins should be assured. In most situations, a standard

multivitamin preparation suffices with the possible excep-

tion of folic acid, which should be replaced at a dosage of at

least 1 mg/day.

Fournier A et al: The crossover comparative trial of calcium acetate

versus sevelamer hydrochloride (Renagel) as phosphate binders

in dialysis patients. Am J Kidney Dis 2000;35:1248–50. [PMID:

10877727]

Strejc JM: Considerations in the nutritional management of

patients with acute renal failure. Hemodial Int 2005;9:135–42.

[PMID: 16191061]

Van den Berghe G et al: Outcome benefit of intensive insulin ther-

apy in the critically ill: Insulin dose versus glycemic control. Crit

Care Med 2003;31:359–66. [PMID: 12576937]

Urea clearance (L/day)

UNA (g/day)

BUN (mg/dL

))

× 100

UNA (g/day)

Protei

nnintake(g/day)

Nonurea nitrogen (g/d

625.

− aay)

UNA (g/day)

BUN BUN

total body water

−

×+

100

UUUN



CHAPTER 13

334

DIALYTIC THERAPY FOR THE CRITICALLY

ILL PATIENT

Renal replacement therapy can provide homeostasis of fluid,

electrolyte, acid-base, and nitrogen balance. Consequently,

the initiation of renal replacement therapy should be consid-

ered whenever any of these factors cannot be controlled with

other therapy. At present, three types of renal replacement

treatment are available for the patient with acute renal fail-

ure: intermittent hemodialysis, peritoneal dialysis, and con-

tinuous renal replacement therapy (CRRT) (Table 13–12).

The particular therapy chosen is often dictated by the

patient’s condition (eg, massive fluid overload, hypercatabo-

lism, or vascular instability) and associated morbid states

(eg, respiratory compromise, hemorrhagic risks, or abdomi-

nal surgery). Aside from these needs, the patient’s baseline

requirements for fluid and solute removal depend on nutri-

tional intake and residual renal function.

Using conventional techniques, machine-driven

hemodialysis is best suited for the hemodynamically stable

patient in whom solute balance is the major concern and

rapid fluid removal is well tolerated. Peritoneal dialysis is pre-

ferred in the patient with significant hemorrhagic risk and in

whom vascular access is difficult to obtain. Continuous

hemofiltration and its related techniques are best for provid-

ing fluid removal in the patient with vascular instability or

massive fluid overload. Despite these generalizations, with

appropriate technical modifications, adequate renal replace-

ment therapy can be provided by any of these methods.



Indications for Dialytic Therapy

Fluid Overload

Poorly tolerated volume overload is the most evident indica-

tion for initiating renal replacement therapy. In general, the

need to relieve pulmonary vascular congestion is the most

pressing issue. It should be noted that even massive amounts

of peripheral edema may be appropriate for the patient’s

condition (ie. hypoalbuminemia or vasodilatory shock), and

fluid removal may cause intravascular volume depletion,

hampering the return of endogenous renal function. When

hypotension is associated with edema and apparent pul-

monary congestion, pulmonary artery catheter monitoring

can be invaluable in determining the amount of fluid that

can be removed safely.

Time-Averaged

Urea Clearance Protein Loss

Treatment Prescription mL/min L/day L/week g/day

∗

Hemodialysis

†

3 × 4 h/week

7 × 4 h/week

14.3

33.3

144

336

Peritoneal dialysis 2 L/h 26.7 24 168 30

CAPD

2 L/6 h

‡

6.9 10 70 10

CAVH 14 L/day 9.7 14 98 15

CAVHD 1–2 L/h 19–35 29–51 189–357 11

CVVH 1–3 L/h 17–50 24–72 168–504 18–36

CVVHD 1–3 L/h 19–52 27–75 189–525 18–36

∗

Includes amino acids and peptides. Published data have been adjusted to account for increased porosity of currently available dialyzers.

†

Assumes average urea clearance of 200 mL/min.

‡

Assumes 3 L/d net filtrate.

Key: CAPD = chronic ambulatory peritoneal dialysis

CAVH = continuous arteriorvenous hemofiltration

CAVHD = continuous arteriorvenous hemodialysis

CVVH = continuous venovenous hemofiltration

CVVHD = continuous venovenous hemodialysis/hemodiafiltration

Modified from Kaplan AA: Dialysis and other extracorporeal therapy for acute renal failure. In: Current Therapy in Nephrology and

Table 13–12. Renal replacement therapies: urea clearance and protein losses.



RENAL FAILURE

335

In the hemodynamically stable patient, intermittent

hemodialysis can provide the most rapid removal of fluid by

easily removing 1–2 L of fluid per hour by ultrafiltration. In

patients with vascular instability, one of the continuous ther-

apies is more appropriate because modest rates of fluid

removal can proceed steadily throughout the day. For exam-

ple, peritoneal dialysis can provide for the gentle removal of

the 2–3 L/day necessitated by intravenous medications and

hyperalimentation. Excessive net fluid removal (>5–10

L/day), however, may lead to hypernatremia because fluid

removed by peritoneal dialysis is hyponatric when compared

with plasma. In patients presenting with massive fluid over-

load, continuous hemofiltration offers the best-tolerated

treatment because the ultrafiltrate is isosmotic. A reasonable

combination of treatments would employ several days of con-

tinuous hemofiltration to achieve normovolemia, followed by

intermittent hemodialysis to provide maintenance therapy.

Electrolyte Abnormalities

Electrocardiographic changes caused by hyperkalemia

should be treated initially with nondialytic therapy (eg, cal-

cium, glucose, and insulin). The only renal replacement ther-

apy capable of rapid potassium removal is machine-driven

hemodialysis, providing clearance rates of 150–250 mL/min

or more (see Table 13–11). Neither continuous hemofiltra-

tion nor peritoneal dialysis can achieve potassium clearance

rates much above 20–40 mL/min, and both these continuous

therapies are best reserved for normalization of modest lev-

els of hyperkalemia or for maintaining potassium balance.

Toxic serum levels of calcium, magnesium, or phosphate

are also most rapidly corrected with machine-driven hemodial-

ysis. Once normal levels are achieved, any of the renal replace-

ment therapies can maintain homeostasis if nutritional intake

is limited and magnesium-containing phosphate binders are

avoided. Renal replacement therapies using dialysate (ie,

hemodialysis, peritoneal dialysis, or continuous hemodialysis)

may contain calcium concentrations of 3.5 meq/L (1.75 mmol/L

of ionized calcium) in the dialysate. Therefore, successful and

rapid treatment of hypercalcemia requires lower dialysate cal-

cium concentrations of 2.5 meq/L (1.25 mmol/L) or less.

Severe hypophosphatemia may complicate all renal replace-

ment therapies, especially in patients being maintained on

intravenous hyperalimentation devoid of phosphate.

Acid-Base Abnormalities

Uremic acidosis rarely generates more than 50–100 mmol

acid per day and can be easily corrected by any of the renal

replacement techniques. Severe uremic acidosis is encoun-

tered most often as a presenting abnormality of unattended

chronic renal failure. Under these conditions, hemodialysis

can provide the most rapid correction of acidosis, but aggres-

sive hemodialysis may precipitate a dysequilibrium syn-

drome. Despite associated hyperkalemia, the dialysate bath

composition should include at least 2 mmol/L potassium

because correction of acidosis causes a substantial lowering

of serum potassium concentration. Consideration also

should be given to a relatively low-calcium bath (2.5 meq/L)

because overly aggressive correction of long-standing

hypocalcemia may precipitate nausea, vomiting, muscle

cramping, and hypertension.

Lactic acid may be produced at rates of up to 50 mmol/h

and usually is associated with severe hemodynamic instabil-

ity. Although daily hemodialysis can provide adequate

replacement of lost bicarbonate, the patient may be left with

rapidly worsening acidosis during the interdialytic period.

Continuous hemofiltration can provide continuous correc-

tion of acidosis and may be best for managing the fluid over-

load often associated with shock and its treatment.

Replacement solutions containing 150 mmol/L bicarbonate

can provide as much as 100 mmol/h of continuous buffer

replacement, but required calcium replacement must be

administered in a separate solution. Peritoneal dialysis, with

exchanges at 2 L/h, can provide approximately 25 mmol

buffer per hour. Dialytic solutions containing lactate should

be avoided because conversion to bicarbonate may be slowed

in patients with circulatory impairment.

Uremia

Although urea is not universally accepted as a uremic toxin,

its levels are used most commonly to judge the degree of ure-

mic toxicity. Several studies suggest that maintaining predial-

ysis BUN at or below 120 mg/dL (43 mmol/L) is beneficial

for overall survival, and it is no longer acceptable to tolerate

excessively high urea levels prior to initiation of renal

replacement therapy. There is good or better evidence to sug-

gest that proper protein-calorie nutrition is also beneficial.

Thus it is inappropriate to withhold adequate nutrition in

order to avoid the associated increase in nitrogen and fluid

intake. On empirical grounds, when pericarditis,

encephalopathy, or hemorrhage is associated with BUN lev-

els above 100 mg/dL, it is hard to argue that such symptoms

are not at least partially the result of retained uremic toxins.

With the preceding considerations in mind, it is reasonable

to initiate renal replacement therapy when BUN is above

100 mg/dL (36 mmol/L). Nonetheless, if rapid return of

renal function is anticipated (eg, in the presence of prerenal

azotemia or obstructive uropathy), levels of 150 mg/dL

(54 mmol/L) or more may be tolerated for a limited period.

Specific indications for dialytic therapy for complications

of uremia include uremic encephalopathy, pericarditis, and

uremic platelet dysfunction. Slowed mentation, somnolence,

and convulsions are part of the uremic syndrome and are

usually associated with other neuromuscular manifestations,

including asterixis, myoclonus, and muscle twitching. In gen-

eral, these symptoms respond within several days after the

start of dialytic therapy.

Despite the existence of massive pericardial effusions,

patients with uremic pericarditis may present with hyper-

tension and pulmonary congestion. The treatment of ure-

mic pericarditis often presents two distinct problems:



CHAPTER 13

336

removal of fluid in the face of potentially compromised

hemodynamics and definitive treatment of the pericardial

inflammation. Initial rapid fluid removal with hemodialysis

may be well tolerated, but as volume removal proceeds,

intravascular pressures may become inadequate to maintain

intracardiac filling, and severe hypotension may result. Thus

normovolemia should be achieved with gentle fluid removal

and anticipation of rapid declines in blood pressure.

Although the toxins responsible for uremic pericarditis have

not been identified, it has been shown empirically that

aggressive solute removal can lead to resolution of pericardi-

tis. Hemodialysis performed five times weekly is recom-

mended, but means to limit anticoagulation should be

employed in order to minimize the risk of hemoperi-

cardium. In patients with large pericardial effusions, early

use of pericardiotomy may be recommended because

aggressive hemodialysis may be associated with a high mor-

tality rate. In one retrospective report, peritoneal dialysis

was found to be superior to hemodialysis in avoiding the

need for surgical drainage. Peritoneal dialysis also avoids the

risk of anticoagulation.

Uremic platelet dysfunction is identified most often with

prolongation of the bleeding time. In general, bleeding times

will normalize along with lowering of serum urea. Acutely,

rapid correction of platelet dysfunction can be achieved with

infusions of desmopressin at a single dose of 0.3 μg/kg.



Drug Dosing During Renal Replacement

Therapy

Many renally excreted medications require dosage modifica-

tion to account for the amount removed by a given renal

replacement therapy. Unfortunately, most of the published

data are of questionable accuracy as a result of variability

between patients and the great differences in clearance rates

achievable with each technique. Four factors govern the

removability of a given drug: molecular weight, degree of

protein binding, volume of distribution, and endogenous

plasma clearance. In general, hemodialysis can offer the

most rapid clearance rates for a low-molecular-weight drug

(<500 kDa). Continuous hemofiltration—but not continu-

ous hemodialysis—will efficiently remove drugs with

molecular weights as high as 10,000 kDa or more. Peritoneal

dialysis will eliminate drugs in the range of MW 500–10,000

kDa. Highly protein-bound medications are not substan-

tially removed by any of the renal replacement techniques,

with the possible exception of peritoneal dialysis. In addi-

tion, modifications of the major techniques may profoundly

alter clearance rates because most of the published data were

obtained with more conventional methodology. For exam-

ple, it has been shown recently that the most modern “high

flux” dialyzers can offer substantial removal of relatively

high-molecular-weight drugs (>1500 kDa), thus greatly

changing their dosing requirements as compared with pre-

vious recommendations.

Aronoff GR et al: Drug Prescribing in Renal Failure: Dosing

Guidelines for Adults, 4th ed. New York: American College of

Physicians, 1999.



Stopping Dialysis

Owing to the availability of chronic dialysis, irreversibility of

renal failure is not an acceptable indication for stopping

treatment. Instead, the patient’s wishes and overall clinical

status should be the only considerations in discontinuing

therapy. In general, withholding of dialysis may be consid-

ered when there is evidence of irreversible vital organ failure

or severe cerebral damage. Most forms of acute renal failure

reverse within 8 weeks. If renal failure persists beyond this

period, one should initiate plans for maintenance dialysis

therapy.



Specific Types of Renal Replacement

Therapy in Acute Renal Failure

1. Hemodialysis

Intermittent hemodialysis is the most widely used technique

for acute renal failure. The method of treatment chosen

varies depending on the rate of generation of nitrogenous

wastes and the patient’s tolerance for fluid overload. In gen-

eral, 4-hour treatments performed three times weekly are

sufficient to provide adequate replacement in the oliguric or

anuric patient. Patients with significant residual renal func-

tion may require fewer treatments per week, especially if

renal failure is nonoliguric. Conversely, the patient with

severe hypercatabolism and poorly tolerated fluid overload

may require daily treatments.

The major advantage of hemodialysis is its highly effi-

cient solute removal, thus limiting treatment time and mak-

ing the patient available for other procedures and treatments.

Disadvantages include relatively rapid fluid removal, which

may be poorly tolerated. Other disadvantages of hemodialy-

sis involve the need for large-bore hemoaccess and anticoag-

ulation of the extracorporeal circuit.

Effectiveness of Hemodialysis

Solute clearance and ultrafiltration rates are variable depend-

ing on the blood flows obtained and the dialyzers chosen.

Most modern dialyzers provide 150–250 mL/min of urea

clearance with blood flows between 200 and 300 mL/min.

More rapid solute clearance can be obtained with the newer

more porous filters, especially when operated at blood flows

of up to 400 mL/min or more. Currently available dialyzers

also can produce between 1 and 3 L of ultrafiltrate per hour,

usually limited by the patient’s hemodynamic stability. A rel-

atively gentler type of hemodialysis involves the prolonga-

tion of the treatment in a low-efficiency mode. These slow,

low-efficiency dialysis (SLED) treatments are applied from

8–18 hours at a time and allow for less aggressive fluid