Central-Venous-Pressure–Guided Volume Expansion May Cut Contrast Nephropathy Risk

Pam Harrison

December 15, 2015

BEIJING, CHINA — Central venous pressure (CVP)–guided fluid administration before, during, and after coronary angiography can significantly reduce the risk of of contrast-induced nephropathy (CIN) and major adverse clinical events compared with standard protocols, suggests a new study[1].

Under lead author Dr Geng Qian (Chinese People's Liberation Army General Hospital, Beijing), investigators found that aggressive volume expansion guided by CVP resulted in a significant 46% reduction in the incidence of CIN compared with standard treatment in high-risk patients undergoing coronary angiography.

Specifically, CIN—defined as an absolute increase in serum creatinine (SCr) >0.5 mg/dL (44.2 µmol/L) or a relative increase ≥25% compared with baseline SCr levels during the first 72 hours following the procedure—occurred in 15.9% of the CVP-guided hydration group compared with 29.5% in the control group (P=0.006).

The proportion of patients who had their SCr levels increase >0.3 mg/dL from baseline was also significantly lower in the CVP-guided hydration group, at 19.7% vs 34.8% (P=0.004), as was the percentage of patients whose SCr increased by 0.3 mg/dL, at 3.79% in the CVP-guided hydration arm vs 9.85% in the control arm (P=0.042).

The same CVP-guided approach also reduced major adverse clinical events by 59% compared with the standard treatment protocol.

Importantly, the incidence of acute heart failure, at 3.8% in the CVP-guided group vs 3.0% for the control group, did not differ between the two treatment arms, and the incidence of acute heart failure at 90 days did not differ between the two groups either, at 6.8% vs 7.6% for the aggressive-volume-expansion group vs controls.

"In patients with chronic kidney disease [CKD], hydration is usually performed at a low rate because of the fear of overhydration and pulmonary edema, particularly in patients with impaired left ventricular function," write Qian and colleagues in a report published online December 9, 015 in JACC: Cardiovascular interventions.

"But it should be emphasized that individual hydration—not restricted hydration—can prevent CIN, and hydration volume should be commensurate to CIN risk."

Study Design

The study enrolled 264 patients with CKD and congestive heart failure undergoing coronary procedures and randomly assigned 132 patients to either CVP-guided hydration or to standard hydration in each arm. "We used the 0.9% sodium chloride hydration in all patients," Qian noted.

In the CVP-guided group, the hydration infusion rate was dynamically adjusted according to the CVP level every hour, and the CVP level was monitored by placing a 5-F catheter in the jugular vein where initial CVP levels were recorded in both groups.

According to initial CVP levels, the CVP-guided group were divided into three groups: group 1 with a CVP <6 cmH2O; group 2 with a CVP 6–12 cmH2O and group 3 with a CVP >12 cmH2O.

The rate at which fluid was administered was adjusted based on which group patients were in, with those in group 1 receiving 3 mL/kg/h, those in group 2 receiving 1.5 mL/kg/h, and those in group 3 receiving 1 mL/kg/h.

The mean age of the cohort was 64 years, and the mean estimated glomerular filtration rates (eGFR) were similar in both groups at slightly under 40 mL/min/1.73 m2.

The total mean volume of saline administered to patients in the CVP-guided group was significantly higher at 1827 mL vs 1202 mL for controls (P <0.001).

On the other hand, CVP-guided hydration patients had greater volume of urine output at 1461 mL than controls at 806 mL (P<0.001).

Looking at the volume of fluid each group received, investigators note that group 1 received 500 to 1000 mL, group 2 received 1000 to 1500 mL, while group 3 received >1500 mL.

Corresponding CIN rates were 37.9% for group 1, 31.3% for group 2, and 7.7% for group three.

There was also a strong negative correlation between hydration volume and increase of SCr (P<0.001), study authors add.

"Patients with worse left ventricular ejection fraction (<40%) got more benefit for CIN prevention from hydration guided by CVP dynamic monitoring," Qian noted, with CIN rates being 17.5% for patients with lower ejection fractions compared with CIN rates of 33.3% for those with the higher ejection fractions (P=0.031).

Similarly, CVP-guided patients with the lowest CVP levels of <6 cmH2O had the greatest protection against CIN, where rates were 10.7%, compared with those with the highest CVP levels, where CIN rates reached 37.5% (P=0.045).

Reduce Contrast Administered

In an accompanying editorial[2], Dr Richard Solomon (University of Vermont College of Medicine, Burlington) noted that the main way practitioners can help prevent CIN is to reduce the amount of contrast administered.

"Additional IV administration of isotonic fluids before, during, and after contrast exposure is also considered standard of care," he writes. As he told heartwire from Medscape, the new CVP-guided hydration approach evaluated in the current study is certainly feasible.

It is also consistent with data from the POSEIDON study, which showed that some hemodynamic monitoring of patients either before or during cardiac catheterization allowed physicians to adjust the rate at which IV fluid was administered.

However, the amount of IV fluid administered during the procedure has a direct impact on the amount of urine produced during the time patients are undergoing the procedure as well as during the immediate postprocedure period.

"You don't necessarily get a beneficial effect on reducing the incidence of kidney injury if you give fluid but the fluid doesn't come out," Solomon explained.

"You have to get urine output, and the total amount of urine produced probably correlates best with outcomes."

On the other hand, the more fluid that is administered, the greater the risk that the fluid will induce heart failure, especially in a high-risk patient group that is somewhat fragile already.

"By doing this hemodynamic monitoring, you can basically identify levels of risk, and in the lowest-risk patients, you give more fluid and in the highest-risk people, you give less," Solomon said.

"In this study, the rate of CIN fell significantly as the amount of IV fluid given increased, and no patients developed CIN who received >1700 mL over the study period."

Solomon cautioned, however, that the incidence of CIN is not yet at zero, suggesting that mechanisms unaffected by volume expansion or urine output are contributing to kidney injury following the administration of contrast media, and novel therapies still need to be explored.

The study was funded by the Chinese People's Liberation Army General Hospital and the Chinese People's Liberation Army Postgraduate Medical School in Peking, China. The authors had no relevant financial relationships. Solomon declared he has served as a consultant or on the scientific advisory committee for Ischemix, MediBeacon, PLC Med, and Sonogenix and has received grant support from AbbVie Bayer, Janssen, and Nephrogenix.

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