Hemodynamic Guidance of Hydration Cuts Contrast Nephropathy in Patients With Kidney Disease, Heart Failure

Contrast-induced nephropathy (CIN) can be safely reduced in patients with chronic kidney disease and heart failure undergoing coronary procedures by guiding fluid administration with central venous pressure measurements, a randomized trial shows. Compared with standard hydration, the approach increases the volume of fluid given without worsening risk of acute pulmonary edema.

Despite strong guideline recommendations on the utility of hydration for preventing contrast-induced nephropathy, patients with congestive heart failure often do not receive sufficient fluids due to concerns about increased cardiac preload and pulmonary edema, according to Yundai Chen, MD, of the Chinese People’s Liberation Army General Hospital (Beijing, China), and colleagues.

Reducing fluid volume may avoid pulmonary edema, but inadequate hydration increases the risk of contrast-induced nephropathy in patients with chronic kidney disease. Thus, strategies continue to be explored to find the sweet spot in which kidney injury is reduced without worsening heart failure.

The approach used in the trial may address those concerns, as “[central venous pressure] could objectively reflect change of intravascular volume status and [the] body’s tolerance to aggressive hydration,” Chen et al report online today in JACC: Cardiovascular Interventions.

The researchers used “a very good protocol,” William O’Neill, MD, of Henry Ford Hospital (Detroit, MI), told TCTMD. “It gives you an easier method of following patients without throwing them into overt heart failure, and it’s a pretty simple and very effective way of decreasing contrast nephropathy,” which he called a growing problem in an aging population.

There will always be a risk of causing heart failure with overaggressive fluid administration, but because that can be treated relatively easily with an IV diuretic, “it’s far better to do that than to cause contrast nephropathy which is really a major problem for patients,” he said.

The current trial included 264 Chinese patients (mean age 64 years; 25% women) with chronic kidney disease and congestive heart failure who underwent diagnostic coronary angiography or PCI between February and December 2014. The patients were randomized to standard hydration with normal saline given at a rate of 1 mL/kg/h or hydration guided by central venous pressure measurements obtained with a 5-Fr catheter inserted into the jugular vein.

In the guided group, the initial rate of fluid administration was 3 mL/kg/h in patients with a central venous pressure less than 6 cm H₂O, 1.5 mL/kg/h in those with a pressure of 6 to 12 cm H₂O, and 1 mL/kg/h in those with a pressure greater than 12 cm H₂O. Central venous pressure was reassessed every hour, with the hydration rate adjusted accordingly.

Hydration was started 6 hours before the procedure and continued for 12 hours after completion for all patients. Visipaque (GE Healthcare) was the contrast agent used in the trial.

Strategy Works

Patients in the central venous pressure-guided group received a higher volume of isotonic saline (mean 1,827 vs 1,202 mL) and had an increased volume of urine output (mean 1,461 vs 806 mL; P < .001 for both) compared with those receiving standard hydration.

That translated into a reduction in contrast-induced nephropathy (15.9% vs 29.5%; P = .006), defined as an absolute increase in serum creatinine ≥ 0.5 mg/dL or a relative increase ≥ 25% compared with baseline during the first 72 hours after the procedure. Using different definitions of kidney injury yielded a similar result.

There was an inverse correlation between volume of fluid received and the rate of contrast-induced nephropathy when both trial arms were combined. Nephropathy rates were 37.9%, 31.3%, and 7.7% in patients who received 500 to 1,000 mL, 1,000 to 1,500 mL, and more than 1,500 mL, respectively.

Through 90 days of follow-up, cumulative major adverse events were less frequent in the central venous pressure-guided group than in the standard arm (8.3% vs 20.5%; P = .004). MI and the need for renal replacement therapy were less common in the guided group, and there were no between-group differences in all-cause mortality, acute heart failure, or acute pulmonary edema.

The 9 patients who developed acute pulmonary edema during hospitalization tended to receive less fluid and a higher contrast volume and to have lower LVEF and estimated glomerular filtration rate and higher heart rate and initial central venous pressure.

Overall, patients with contrast-induced nephropathy had a high rate of major adverse events (38%) and a greater risk of all-cause mortality relative to patients without the complication (P = .017).

Is Approach Practical?

Somjot Brar, MD, MPH, of Kaiser Permanente (Los Angeles, CA), told TCTMD that “the study is relevant because it shows that greater volumes of fluid administration do reduce the rates of contrast nephropathy.” That is consistent with the findings of the POSEIDON trial, for which Brar served as principal investigator.

He added that much of the prior research on fluid administration has involved standardized rates before, during, and after the procedure. “These data show that those rates are largely probably inadequate,” he said.

Brar pointed out, however, that the protocol used in the trial is feasible but not practical because of the need for an additional access site to measure central venous pressure. In POSEIDON, hydration was guided by LV end-diastolic pressure, which can be measured at the time of catheterization through existing arterial access sites and gives a more accurate assessment of the development of pulmonary edema, Brar said.

Moreover, he noted, monitoring central venous pressure hourly and making multiple adjustments to hydration rate present challenges in terms of cath lab and hospital workflow.

“But the underlying concept is nevertheless very important,” he said. “These data, along with POSEIDON, highlight that it is safe to administer fluids at a much higher rate and if you use certain metrics to identify patients who are going to have a good probability of tolerating those higher rates, then the risk of developing complications like heart failure can be quite low.”

Unanswered Questions

Brar noted that neither POSEIDON nor the current trial provide information about managing patients with acute decompensated heart failure, who were excluded from both studies and who have a high risk for contrast nephropathy.

Fluid administration is difficult and sometimes contraindicated in these patients, suggesting the need for other solutions, Brar said. One such solution is being evaluated in the ongoing AVERT trial, which has completed enrollment but has not provided results. The trial is testing a device designed to reduce the amount of contrast administered while maintaining good image quality.

In an accompanying editorial, Richard Solomon, MD, of the University of Vermont Medical Center (Burlington, VT), agrees about the need for further research.

“Despite these encouraging results, the incidence of [contrast-induced nephropathy] has not dropped to zero, suggesting that mechanisms unaffected by volume expansion or urine output are contributing to kidney injury following contrast administration,” he writes. “This creates space for additional novel therapies to be explored.”

Sources: 
1. Qian G, Fu Z, Guo J, et al. Prevention of contrast induced nephropathy by central venous pressure guided fluid administration in chronic kidney disease and congestive heart failure patients. J Am Coll Cardiol Intv. 2015;Epub ahead of print.
2. Solomon R. Improving intravenous fluid therapy for prevention of contrast induced nephropathy: how to give more without causing heart failure [editorial]. J Am Coll Cardiol Intv. 2015;Epub ahead of print.

Related Stories:

• POSEIDON: Sliding-Scale Hydration Successfully Prevents Contrast-Induced Nephropathy
• Contrast-Induced Nephropathy Linked to Long-Term Adverse Events
• Regional Quality-Improvement Effort Reduces Contrast-Induced AKI After PCI