Iatrogenic urinary disorders: How can you minimize them?

Mar 01, 2001

Iatrogenic and nosocomial disorders defined

The Greek term "iatros" means physician, and is derived from the word "iasthai", which means to heal or cure.

In modern usage "iatro" connotes a relationship to medical or surgical treatments. The term iatrogenic contains the root word "iatros," and the root word "gennan" which means "to create or produce".

Dorland's Medical Dictionary defines iatrogenic as any adverse condition or complication in a patient occurring as a result of treatment by a physician. Because there is no comparable English word for adverse events in patients resulting from treatment by veterinarians, the word iatrogenic has been adopted by our profession. The fact that iatrogenic is often considered as a pathophysiologic mechanism of disease emphasizes that there are some patients we cannot help, but there are none we cannot harm.

The word iatrogenic is related in concept to the word "nosocomial".

The Greek root word "nosa" indicates a relationship to disease. Nosology is defined as the science of classification of diseases. Dorland's dictionary defines the term nosocomial as a disease (such as an infection) originating in the hospital. The fact that patients can acquire diseases in hospitals emphasizes that there are some patients we cannot help, but there are none we cannot harm.

The word iatrogenic and nosocomial are not synonyms for malpractice. Perhaps our point can be best applied with the following illustration.

In an article written in the February 1, 1999, issue of The New Yorker magazine entitled, "When Doctors Make Mistakes", the deck was, "The real problem isn't how to stop bad doctors from harming, even killing, their patients. It's how to prevent good doctors from doing so."

The central theme of this article embodies the premise that any healthcare provider, including you and me, no matter how experienced or skilled they may be, can unintentionally cause harm to their patients.

The following discussion describes some of the many iatrogenic and nosocomial events that could occur in your patients with urinary tract disorders.

Acute oliguric, nonpolyuric azotemic renal failure

Patients with impaired renal function are at substantial risk for adverse drug reactions.

In general, if drugs with extensive renal elimination are absolutely essential for management of patients with renal failure, some degree of dosage adjustment is usually required.

Dosage adjustment should be considered on a case-by-case basis, after considering concomitant medical conditions, the type of other medications that are being given, and the severity of renal dysfunction.

If dogs with enhanced renal vasoconstrictor activity mediated by volume depletion are given nonsteroidal anti-inflammatory drugs, decreased renal cyclooxygenase activity may further reduce renal perfusion to such a degree that acute renal failure occurs.

The following are examples of conditions that increase the risk of NSAID-induced acute renal failure:

a). hypovolemia associated with deep or prolonged anesthesia.

b). hypoalbuminemia associated with the nephrotic syndrome.

c). reduced cardiac function (i.e. congestive heart failure).

Some studies have been interpreted to suggest that administration of metaclopromide, an anti-dopaminurgic drug, to treat vomiting associated with acute oliguric renal failure may counteract the effects of low doses of dopamine concomitantly given to augment renal blood flow, glomerular filtration and sodium excretion.

Until the clinical significance of this potential complication has been confirmed, it may be wise to consider available alternatives with the goal of avoiding undesired drug interactions.

Excessive administration of parenteral fluids to patients in the maintenance phase of pathologic oliguria with the objective of increasing glomerular filtration often results in over hydration and all of its sequela.

Empirical observations suggest that administration of allopurinol to dogs with renal failure may cause a further decline in renal function.

The concomitant use of furosemide and gentamicin increases the risk of acute renal failure in dogs.

Chronic polyuric azotemic renal failure

Patients with renal impairment are at substantial risk for adverse drug reactions, and are intolerant to many side effects of drugs (See preceding section).

For this reason, drugs should not be given with the mind-set that they might help but will do no harm. The manufacturer's recommendations and description of side-effects should be reviewed before giving any drug to a patient in renal failure.

Drugs containing citrate salts (i.e. potassium citrate and calcium citrate) may enhance unwanted absorption of aluminum contained in drugs such as aluminum carbonate, aluminum hydroxide and sucralfate. Therefore, caution should be used if consideration is being given to using such drug combinations for extended periods.

Because glucocorticoids are catabolic, they may enhance the magnitude of catabolic sequela associated with renal failure. They may also adversely affect protective host immune mechanisms.

Food aversion may be induced if a nauseated or vomiting uremic patient is given a diet designed for long-term management of renal failure.

Food aversion is most likely to occur if nauseated patients are force fed, or if painful sample collection or drug administration are associated with feeding. In general, unpalatable drugs should not be mixed with the primary source of food or water. To minimize the possibility of the patient's aversion to renal failure diets designed for long-term use, they should not be offered to renal failure patients until the underlying causes contributing to anorexia, nausea and vomiting are minimized or eliminated.

Use of rhEPO

Extra-label use of recombinant human erythropoietin (rhEPO) to treat the hypoproliferative anemia associated with chronic renal failure in dogs and cats is associated with benefits and risks. The most significant adverse event resulting from rhEPO therapy in dogs and cats is development of anti-rhEPO antibodies which may result in a nonresponsive decline in RBC production.

Because this adverse event may develop in approximately 50 percent of patients within one to three months from the start of rhEPO therapy, we recommend that use of rhEPO be withheld until the magnitude of the hypoproliferative anemia is substantial ( i.e. PCV = ~20 percent in a normally hydrated patient ) and associated with clinical manifestations of anemia.

Administration of calcitriol to treat renal secondary hyperparathyroidism without first controlling hyperphosphatemia is likely to result in increased morbidity due to mineralization of tissues with calcium phosphate. Likewise, administration of calcitriol without titrating the dosage with serial evaluation of serum calcium and phosphorus concentrations, may result in hypercalcemia and exacerbation of the underlying renal failure.

Use of antihypertensive drugs such as angiotensin converting enzyme inhibitors and calcium channel blockers without titrating the dosage by monitoring blood pressure may result in ineffective or excessive dosages. Excessive dosages may result in 1). hypotension and a further decline in renal function, and 2). adverse drug reactions.

Administration of angiotensin converting enzyme inhibitors impairs release of aldosterone by the adrenal cortex, resulting in reduced renal excretion of potassium. If patients being treated with ACE-inhibitors are also being treated with drugs that contain salts of potassium (i.e. potassium citrate), serum concentrations of potassium should be serially monitored to detect hyperkalemia.

Between meal administration of calcium salts (i.e. calcium carbonate, calcium acetate, calcium citrate) as oral phosphorus binding agents may result in enhanced absorption of calcium predisposing to hypercalcemia. Hypercalcemia may exacerbate renal dysfunction. Therefore, oral phosphorus binding agents should be given with meals. In addition, between meal administration of these drugs will be less effective in preventing intestinal absorption of dietary phosphorus.

Caution should be used in correcting acidemia in patients with chronic renal failure characterized by hypocalcemia because acidemia is associated with a shift of biologically inactive protein bound calcium to biologically active ionized calcium. Correcting the acidemia too rapidly has a potential to reverse this process leading to functional hypocalcemia.


Supplementing dietary protein with the goal of minimizing protein calorie malnutrition caused by protein losing glomerulopathies may enhance the magnitude of proteinuria. Enhanced glomerular proteinuria may exacerbate the magnitude of tubulointerstitial lesions.

Administration of aspirin to minimize platelet aggregation in azotemic nephrotic patients with low plasma concentrations of antithrombin-3 and albumin may result in NSAID induced acute renal failure. Multiple mechanisms may be involved including:

· enhanced renal vasoconstrictor activity mediated by volume depletion due to hypoalbuminemia.

· reduction of renal clearance of aspirin.

·reduced binding of aspirin to albumin with a corresponding rise in concentrations of nonprotein bound active drug.

Glucocorticoids may exacerbate the severity of protein-losing glomerulonephropathy and may enhance the magnitude of catabolic effects of renal failure.

Administration of diuretics for the primary objective of eliminating subcutaneous edema in hypoalbuminemic patients with glomerulonephropathy is detrimental if control of edema is accomplished primarily by inducing dehydration.

Urinary tract infections

There appears to be an increase in the prevalence of nosocomial bacterial urinary tract infections with multiple antibiotic resistant bacteria, especially in veterinary intensive care units where antibiotics and indwelling transurethral catheters are frequently used to treat multiple patients in close proximity.

Therefore, transurethral catheters should only be used when the probable benefits exceed the risks of iatrogenic and nosocomial disease.

Collection of voided urine by manually compressing the urinary bladder through the abdominal wall may force urine containing pathogens into the ureters and renal pelves as well as the urethra.


Several drugs may augment the morbidity associated with urolithiasis. They include:

· drugs that promote hypercalciuria (acidifiers, calcitriol, corticosteroids, furosemide, and those that contain substantial quantities of sodium).

· drugs that may decrease the solubility of potentially lithogenic substances (urine acidifiers and alkalinizers).

· ascorbic acid which may augment hyperoxaluria.

· allopurinol which may augment xanthinuria.

· drugs and their metabolites that may crystallize to form a portion of uroliths (sulfadiazine, fluroquinolones, primidone, tetracycline, urographic contrast agents, magnesium trisilicate and phenazopyridine).

Nephrotomies performed to remove uroliths may cause varying degrees of nephron destruction as a result of transection of renal arteries. Thus the risk/ benefit ratio of nephrotomies must be assessed, especially if the patient has evidence of concomitant renal disease or renal dysfunction.

Feline lower urinary tract disease

The benefits of performing exploratory cystotomies to evaluate cats with idiopathic lower urinary tract disease uncommonly change the therapy or course of the underlying disorder. In other words, the benefits of exploratory cystotomies in these patients uncommonly justify the associated morbidity and expense.

Use of buffered acetic acid (Walpole's solution) in attempt to dissolve struvite crystals in urethral plugs may impair the ability of protective glycosaminoglycans to prevent adherence of bacteria and crystals to the urothelium.

Use of indwelling transurethral urinary catheters may increase morbidity by:

a) causing trauma, especially if they are inflexible, and if they are over inserted.

b) inducing a "foreign body" inflammatory response in adjacent tissues.

c) enhancing the rate of urethral strictures if used in the post-operative management of perineal urethrostomies.

Treating chronic recurrent feline lower urinary tract disease by cauterizing of denuding the bladder mucosa is likely to exacerbate the magnitude of hematuria, pollakiuria and dysuria, and prolong recovery time.

Treatment of urethral obstructions by perineal urethrostomy is associated with increased risk of bacterial urinary tract infections and urethral strictures.


Iatrogenic and nosocomial urinary tract disorders are not limited to "dangerous" doctors. They are also caused by highly competent specialists. What is the solution to this problem? It does not lie in revoking or restricting their licenses to practice veterinary medicine. Why? Because, this approach promotes secrecy and an unwillingness to share our mistakes with colleagues with the goal of understanding and preventing them.

What is needed first are practical mechanisms to detect and define the underlying events related to iatrogenic and nosocomial diseases. They should be designed to fix the fault and not the blame. Once the magnitude and nature of related events are identified, efforts can then be directed toward minimizing them.

But what about urinary tract diseases for which the risk/benefit ratios of various treatments cannot be clearly forecast? What then?

When uncertainty exists as to whether or not a particular drug, medical or surgical procedure is or is not in the best interests of the patient, we try to answer the following questions.

Based on all information available, would I choose this course of therapy if I were this patient?

Based on knowledge of my own skill and experience, and the availability of support staff and the ability to monitor therapeutic response, would I consent to the proposed plan of therapeutic action if I were in this patient's exact situation? What therapeutic goals are likely to be achieved?

If I do follow the proposed plan of therapy, in all probability will the overall benefits of this plan justify the associated risks and costs?

Dr. Osborne, a diplomate of the American College of Veterinary Internal Medicine, is professor of medicine in the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota.