Published in the August 2007 issue of Today’s Hospitalist.
The elderly heart patient has been admitted to the hospital with paroxysmal nocturnal dyspnea (PND) and increased leg swelling. She regularly takes the water pill furosemide (Lasix), the ACE inhibitor lisinopril and glipizide for her diabetes.
In addition to some bilateral rales and some edema, her baseline creatinine is 2.2, which, when converted to a glomerular filtration rate (GFR), equals 24 ml/min. She is clearly in stage 4 of the five stages of chronic kidney disease (CKD).
Add up the patient’s comorbidities, and this patient “is going to be very difficult to diurese,” explained Suzanne G. Watnick, MD, assistant professor in the division of nephrology at Oregon Health and Science University in Portland, Ore.
Dr. Watnick, who is also medical director of the dialysis unit at the Portland Veterans’ Administration Medical Center, presented the case of this 68-year-old woman as a springboard to offer some time-tested tips and new insights into caring for renal patients who are difficult to diurese. Here are some of the highlights of her presentation, which she gave at a Spring 2007 Hospitalist CME series meeting this year.
When it comes to diuresing difficult patients, Dr. Watnick said that an important starting place is to realize that patients with chronic kidney disease will need higher doses of loop diuretics, such as furosimide, to achieve diuresis and natriuresis.
She offered a fairly simple strategy to ensure that patients are getting adequate dosing: An hour or two after you’ve given an IV dose of a loop diuretic, ask patients or nurses if they are seeing a brisk diuresis. If patients aren’t urinating within two hours of the drug’s administration, “they are not responding,” Dr. Watnick said, “and you have to up the dose.”
Another important point? By the end of the day, the drug will likely start to wear off. If that happens, she explained, the patient will start retaining all the water and sodium you’ve been trying to get rid of. To avoid this so-called “braking phenomenon,” Dr. Watnick recommends ordering twice daily (BID) dosing after reaching a single dose that works.
And if intermittent dosing isn’t working well, consider changing patients to a continuous infusion of the diuretic. Patients with chronic kidney disease, Dr. Watnick explained, are going to need higher doses because it’s going to be harder for the drug to reach its site of action in the thick, ascending limb of the loop of Henle.
If you’re ordering a continuous infusion of Lasix, Dr. Watnick suggested starting with a loading dose of 80 to 120 mg and setting the continuous hourly dose based on the patient’s GFR.
Diuresis additives and alternatives
According to Dr. Watnick, additives to loop diuretics can enhance their action. Thiazides, for example, work especially well in patients who have been on chronic loop diuretics, because they have an overabundance of channels in the distal convoluted tubule to reabsorb sodium. Thiazides block these sodium channels distally, so they can induce a brisk diuresis.
There is a caveat, however. She noted that because loop diuretics used this way can raise renin levels “and aggravate cardiovascular abnormalities in patients with already compromised cardiovascular systems “”you need to be very cautious” during the initial period of loop diuretic administration in the hospital. Dr. Watnick added that eventually, after an hour or so, a patient’s heart rate, systemic vascular resistance, mean arterial and left ventricular end-diastolic pressure should all return to baseline levels.
For patients who are especially hard to diurese, she said, one alternative is hemofiltration. New technologies now permit hemofiltration to be performed via an IV with specialized machines instead of traditional hemodialysis catheters and machines. From a cardiovascular perspective, Dr. Watnick said, hemofiltration seems to result in better long-term outcomes for diuretic-resistant patients.
Another group of difficult-to-diurese patients are individuals with nephrotic syndrome. Dr. Watnick said that’s true even of individuals who have a relatively preserved GFR.
Because nephrotic syndrome requiring aggressive diuresis can mimic congestive heart failure, Dr. Watnick urged hospitalists to remember to check urine protein and creatinine levels for inpatients. It’s not necessary to collect and analyze a 24-hour urine sample, she said. A spot urine protein/creatinine ratio is a good proxy for a 24-hour urine collection.
What about the patient with kidney disease who needs coronary angiography? Is the common practice of sheltering such patients from the risks of contrast-induced nephropathy causing these patients harm?
Dr. Watnick suggested that physicians are so overcautious about contrast that some patients are not receiving life-saving angiography. “Renalism” “discriminating against patients with chronic kidney disease “drives the inappropriately low rates of angiography that have been charted in several studies, Dr. Watnick said.
She reminded hospitalists that the most frequent cause of death for people with chronic kidney disease is cardiovascular disease, not end-stage renal disease. “These are the people in whom you have to do appropriate cardiovascular interventions,” she explained.
There are a number of steps physicians can take to prevent many instances of contrast-induced nephropathy. These include advocating for patients with radiology staff about the best types and doses of contrast dyes to use, making sure that patients receive appropriate saline and providing other drugs prophylactically. The goal is to ensure that patients who need radiographic studies can get them, she said.
While the risks of dye nephropathy in the general population may be low “0.6% to 2% “they can be much higher for certain patients, particularly for those with chronic kidney disease and diabetes. For these patients, Dr. Watnick said, the risk can be as high as 50%.
In addition, she said, for most people, contrast-induced nephropathy is usually thought to be a benign problem, with 95% of patients recovering within two weeks. For the small number of patients with more lasting contrast-induced nephropathy, however, the exposure can be deadly. Acute renal failure raises the risk of one-year mortality four- to five-fold. “This is something you really want to be protecting your patients from,” she said.
Patients at high risk
Exposing patients to contrast agents can increase serum creatinine in the short-term. It usually happens within 24 to 48 hours of exposure to the contrast agent, so a patient whose serum creatinine starts to rise four or five days after a study probably does not have contrast-induced nephropathy, Dr. Watnick said.
In addition to those with chronic kidney disease (particularly, a GFR lower than 70 ml/min) and diabetes (especially those with proteinuria), patients who have the greatest risk of developing the problem are those who have congestive heart failure, hypotension, multiple myeloma or are older. New studies, she said, have added to this high-risk category those patients who need urgent percutaneous coronary intervention, those with peripheral vascular disease and those receiving a contrast medium load of greater than 250 ml.
“The incidence of contrast-induced nephropathy really does increase with the number of risk factors,” Dr. Watnick said.
Because the type and quantity of contrast volume can change risks, hospitalists should talk to radiologists and technicians about what can be done to limit the dye in patients who have other risk factors. Sometimes, she said, dyes can be diluted, and ventriculograms can be avoided. Selecting a type of dye with lower serum osmolarity can help.
Although the FDA in May issued a warning about using the dye gadolinium because some patients have developed a painful, debilitating skin disease called nephrogenic systemic fibrosis, Dr. Watnick told hospitalists that problems have been seen mainly with patients with very severe (stage 5) chronic kidney disease, meaning their GFR is 15 or less.
“You should avoid this agent definitely if their GFR is less than 15,” she said. But if their kidney disease is less severe and they need the study, discussing with the radiology department the pros and cons of using the dye is warranted.
In terms of prophylaxis against contrast-induced nephropathy, Dr. Watnick said, studies have found that while certain agents can help “including sodium chloride, N-acetylcysteine, sodium bicarbonate and potentially methylxanthine “others are ineffective or even harmful. Agents like furosemide, mannitol, dopamine, calcium channel blockers and hemodialysis following a contrast load can sometimes worsen outcomes, she explained.
And while ACE inhibitors are currently being studied, Dr. Watnick said she tries to continue the ACE inhibitor if the patient is not having any kidney-related issues with it. She stops the medication only if the patient’s serum creatinine levels start to rise.
“Do not force diuresis in patients who have just had contrast,” she said. Instead, focus on making sure that patients are volume replete before and after they get their contrast load. Isotonics are preferred over hypotonic solutions, she said, and IV administration is preferable to oral.
When possible, she recommended giving patients a milliliter per kilogram of normal saline per hour for up to 12 hours pre- and post-procedure. If you have only two or three hours, she urged physicians to “still try to get a liter in if you can, watching their volume status.”
Although at least one randomized controlled trial recently showed that giving CKD patients sodium bicarbonate (3 ml/kg/hour for one hour before and 1 ml/kg/hour for six hours after a contrast-using procedure) instead of normal saline resulted in less risk of contrast-induced nephropathy, there is a downside. Some patients develop significant skin necrosis at the site of the sodium bicarbonate administration.
“No one will fault you for just using normal saline as opposed to sodium bicarbonate, even in a high-risk patient,” Dr. Watnick said.
Other than watching volume and talking to the lab about limiting the dose and osmolarity of the dye used, Dr. Watnick said, the best prophylactic measures are making sure patients are free of possible toxins before and on the day after the procedure. These include NSAIDs, diuretics and metformin. There is no clear benefit from vasodilators.
Using N-acetylcysteine (a thiol-containing antioxidant) is common and may help, but its mechanism for preventing contrast-induced nephropathy is unclear. Of the 12 meta-analyses of the practice, moreover, only nine suggested benefit, and many produced inconclusive results. A recent study, however, suggested there may be a benefit to giving a high dose of N-acetylcysteine intravenously right before a patient goes to the cath lab.
“Despite a paucity of data, physicians are using this, nephrologists included,” she said. “It may be beneficial.”
Deborah Gesensway is a freelance writer reporting on U.S. health care from Toronto, Canada.
Avoiding contrast-induced nephropathy in CKD patients
To avoid “renal discrimination” “a problem that occurs when physicians worried about contrast-induced nephropathy withhold coronary angiography “hospitalists can use the following seven-step algorithm. It was presented by Suzanne G. Watnick, MD, assistant professor in the division of nephrology at the Oregon Health and Science University, at a recent Hospitalist CME series meeting.
1. Identify high-risk patients.
2. Consider alternative radiographic tests or determine whether the study can be avoided.
3. Focus on volume repletion using normal saline. Consider using sodium bicarbonate if your hospital has a good protocol to avoid the potential of skin necrosis at the IV site.
4. Limit dye dose, and select iso-osmolar contrast if possible.
5. Discontinue potentially harmful medications that can co-induce acute renal failure just before and after the procedure.
6. Monitor serum creatinine levels and follow these patients’ renal function.
7. Avoid discriminating against patients with chronic kidney disease.
Another tough case: glomerulonephritis
Patients with potentially rapidly progressive glomerulonephritis would normally end up on a nephrology service. But in hospitals too small to support a renal service, patients who undergo a renal biopsy for the disease likely will fall into the purview of hospital medicine.
According to Suzanne G. Watnick, MD, assistant professor in the division of nephrology at the Oregon Health and Science University, data from recent studies should be of interest to hospitalists. The current thinking, she said, is to regularly admit renal biopsy patients to the hospital overnight following a biopsy to look for the common complications of pain, bleeding and even death.
Dr. Watnick advised hospitalists to watch these patients carefully, ordering them flat on their backs for four to six hours after the biopsy and referring any complicated cases to hematology. They should be off their anticoagulants, including aspirin, for at least a week.
“You really need to watch,” she said, “because the bottom line is that a patient with a renal biopsy is a bleeding patient because renal arteries are easier to hit” and hemostasis is difficult to achieve.