Wednesday, June 12, 2013

Contrast Induced Nephropathy, N-acetylcysteine, and Trauma

The risk of contrast induced nephropathy (CIN) in cardiac patients undergoing primary cardiac catheterization is approximately 5%.[1] With associated risk factors (Table), that risk can jump to 50%.  Pertaining to cardiac cath, administration of high volumes of contrast intra-arterially confers a higher risk compared to patient populations such as trauma patients who require radiologic imaging with contrast.[2]  Additionally, while similar risk factors may be present, trauma patients tend to be younger and generally healthier compared to patients requiring emergent cardiac interventions.  But there are times when interventions to prevent CIN are considered in an effort to counter balance risk factors.

Assessing the use of NAC for CIN prophylaxis in trauma patients is difficult. Difficult in the sense of evidence based medicine.  While a plethora of studies exist, few examine populations other than cardiac catheterization patients.  It is possible to correlate existing data to other populations such as trauma patients, but less than ideal due to poor quality evidence.

Echoing both the population limitations and quality of evidence, the most recent meta-analysis of the NAC in CIN data is centered on patients undergoing cardiac catheterization.[3] Small, varied population with a potpourri of dosing regimens limits the pooling of the data. Not surprisingly, no clear reduction in the risk of CIN was found. Importantly, though reduction in the incidence of CIN may be the most obvious end point, it is not the most relevant.  No study has been appropriately powered to assess for mortality.

Consistent with the varied data, the exact mechanism of NAC for CIN prophylaxis isn’t known. NAC is thought to counteract the contrast media induced increased production of renal endothelin, prostaglandins and adenosine leading to renal vasoconstriction, and provide anti-oxidant effects to mediate direct renal epithelial injury and free radical production.[4]  If the theorized mechanisms of CIN and NAC hold true, NAC would be an ideal agent base on its proposed benefit and safety (though dependent on dosing).

While some studies evaluated doses of NAC that mirror APAP toxicity dosing, lower doses are *effective* (based on available data).[5,6] Doses ranging from 600 mg to 1200 mg every 12 hours limit the risk of deleterious effects of high doses of NAC, namely cerebral edema.  Oral administration is preferred, but IV administration can be used and for trauma patients who may not be able to receive oral medications. But despite the higher cost of IV NAC, each patient should be assessed for risk of CIN based on known risk factors and consideration for their immediate medical problems.  Unnecessary use of medications that could potentially delay the patient from receiving critical imaging in trauma is polypharmacy and inappropriate. 

In reality, despite poor evidence, we often find ourselves settling for covering-your-ass.  In this setting, the calculated risks seem to tilt toward just giving NAC and musing over the data on rounds.  On the other hand, other bloggers have said that eminence based medicine isn’t such a bad thing. In this situation, though I’m not sure this is eminence based, perhaps logic based: plausible mechanisms, despite poor data.

Existing renal dysfunction
Age > 75
Diabetes mellitus
Heart failure (LV dysfunction)
Myocardial infarction
Hemodynamic instability
Concurrent nephrotoxic agents
High-osmolality contrast
High-volumes of contrast

  1. Thomsen HS, Morcos SK. Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines. Br J Radiol. 2003;76(908):513-518
  2. Hipp A, et al. The incidence of contrast-induced nephropathy in trauma patients. European Journal of Emergency Medicine 2008, 15:134–139
  3. Sun Z, Fu Q, Cao L, Jin W, Cheng L, et al. (2013) Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized, Controlled Trials. PLoS ONE 8(1): e55124.
  4. Drager LF, Andrade L, Barros de Toledo JF, Laurindo FR, Machado Cesar LA, Seguro AC. Renal effects of N-acetylcys- teine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury. Nephrol Dial Transplant. 2004;19(7):1803-1807.
  5. Baker CSR, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid pro- tocol for the prevention of contrast-induced renal dysfunction: the RAPPID study. J Am Coll Cardiol 2003;41:2114-8.
  6. Marenzi G, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 2006;354:2773-82

Featured Post

Giapreza - A Closer Look at the Pharmacology of Ang2

Angiotensin-II (Ang2) is now an FDA approved vasopressor. With this new addition to the available options, experts are combing over the ...