Pre-oxygenation Reduces Contrast Nephropathy in Elective PCI Patients

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Oxygen administration prior to elective angiography or percutaneous coronary intervention (PCI) reduces contrast-induced nephropathy (CIN), according to results posted online May 8, 2013, ahead of print in the Journal of the American College of Cardiology.

Researchers led by Yukio Tsurumi, MD, PhD, of Yokohama General Hospital (Kanagawa, Japan), randomized 426 patients undergoing elective angiography and/or PCI to pre-oxygenation (n = 174) or a control group (room air; n = 175). All patients also received hydration with isotonic saline. Oxygen was administered via nasal cannula, 2L/min from 10 minutes before the procedure to the procedure’s end.

Dr. Tsurumi and colleagues theorized that contrast medium may contribute to intrarenal hypoxia and renal ischemia, and that sufficient oxygenation prior to contrast exposure along with saline hydration may prevent CIN more effectively.

Factors including contrast volume, serum creatinine concentration, and eGFR were similar between the 2 groups. Partial pressure of oxygen (PaO₂) at baseline was higher in the pre-oxygenation group than in controls (134 mm Hg vs. 90 mm Hg; P < 0.001), with no differences in PCO₂, HCO₃^-, base excess, or lactate. Thus, the researchers note, systemically higher PaO₂ concentrations in arterial blood were achieved prior to contrast administration without CO₂ narcosis at an oxygen concentration of 2 L/min.

CIN Rate Lower With Oxygen

The overall rate of CIN, defined as an increase in serum creatinine concentration ≥ 25% above baseline at 48 hours after contrast administration, was 2.9%, occurring less frequently in the pre-oxygenation group (0.6% vs. 5.1%; OR 0.11; 95% CI 0.01-0.85; P = 0.01).

The majority of CIN patients (8 of 10) were chronic kidney disease stage III or worse (eGFR < 60 mL/min/1.73m²). On univariate analysis, low eGFR (< 60 mL/min/1.73m²) and low PaO₂ (< 100 mm Hg) were associated with increased risk for CIN. On multivariable analysis, eGFR (OR 4.12; 95% CI 1.0-16.6; P = 0.046) and PaO₂ (OR 12.61; 95% CI 1.6-101.3; P = 0.017) were still predictors of CIN.

In 6 out of 10 CIN patients, elevated serum creatinine did not recover to baseline levels at 6-month follow-up.

“The present study thus demonstrated that oxygen preconditioning concomitant with standard hydration decreased the occurrence of CIN in patients undergoing cardiovascular angiography,” the researchers conclude, adding that “this protective effect was more pronounced in patients with chronic renal insufficiency.”

The researchers add that there were no side effects from pre-oxygenation. They note that while little is known about the underlying cellular mechanisms of CIN, renal hypoxia and concomitant release of reactive oxygen species have been considered important mechanisms of renal injury mediated by contrast. Reduced effective renal cortical-medullary blood flow and afferent arteriole constriction may reduce oxygen supply while increased reabsorption due to osmotic load and microvascular damage may increase renal oxygen consumption.

Pre-oxygenation may, therefore, attenuate contrast-mediated renal damage brought on by the imbalance between oxygen supply and demand.

Theory Needs Explaining

However, Somjot S. Brar, MD, MPH, of Kaiser Permanente (Los Angeles, CA), was not convinced by the results. “It isn't clear to me how or why administration of 2 L of nasal cannula [oxygen], increasing the PaO₂ by a modest amount from 90 to 134, could yield a reduction in the contrast nephropathy rate,” he told TCTMD in an e-mail communication.

He also noted that the overall incidence of CIN in the study was very low. “This was a very low risk cohort. The event rate was considerably lower than what has been observed in multiple other trials,” Dr. Brar said. “Recruitment of patients at risk of contrast nephropathy (eGFR < 60 and/or CIN risk factors) often yields contrast nephropathy event rates of 10-20%. While the findings reach statistical significance, I worry that the results are not very robust. It is possible that one additional event in the intervention arm would yield a nonsignificant overall result.”

Dr. Brar called the results “interesting,” but cautioned they need to be validated and replicated before adoption into routine care.

The possible mechanism behind them needs explaining, too. “The theory is not clear to me,” Dr. Brar said. “I am not aware of an animal model that would support the hypothesis; however, CIN animal models are limited.”

Future studies, he said, should be in patients at higher risk of CIN (eGFR < 60 or CKD stage III or greater).

Study Details

Continuous infusion of 0.9% saline (1 mL/kg/hr) was administered 12 hours before the procedure until 12 hours following the procedure in both groups.  Almost two-thirds of the patients (64.8%) were over age 70 years.

 

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Source:
Sekiguchi H, Ajiro Y, Uchida Y, et al. Oxygen preconditioning prevents contrast-induced nephropathy (OPtion CIN study). J Am Coll Cardiol. 2013; Epub ahead of print.

 

Disclosures:

• Drs. Tsurumi and Brar report no relevant conflicts of interest.

 

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