What is the potential problem in patients undergoing therapy with metformin-containing medications receiving I.V. iodinated contrast?
There is a risk of life-threatening lactic acidosis, termed “MALA” (metformin-associated lactic acidosis).This is rare, with an incidence of 1-2/100,000 per year. This accounts for 0.1-1% of all patient admitted to the ICU. Mortality is high (30-50%). Until recently, it is for these reasons that all patients discontue metformin-containg products following iodinated contrast administration. The mechanism is felt to be due to a combination of lactic acid formation from glucose in the splanchnic bed, intracellular shift from aerobic to anaerobic metabolism, and inhibition of gluconeogenesis from lactate(via inhibition of pyruvate carboxylase – the rate limiting enzyme in the formation of glucose from lactate).
Fortunately, there has been reconsideration and re-evauation of the true risk factors for developing MALA. Research has shown that nearly all cases of MALA occur in patients withhemodynamic instability (hypotension) and a metabolic disorder related to the liver and/or kidneys. Furthermore, there is controversy regarding the causal relationship between diabetes and MALA (i.e. MALA may be incidental in DM pateints). This has lead to a much more appropriate and evidenced based approach to management of metformin-treated patients undergoing iodinated contrast examinations. The ACR has revised its metformin recommendations in the current and previous editions of the ACR Contrast Manual (http://www.acr.org/quality-safety/resources/contrast-manual), versions 8 and 9 (see below).
What does this mean for metformin-treated patients in need of an iodinated contrast exam?
For nearly all patients in the outpatient setting, we will no longer need to withold metformin following iodinated contrast administration. This is a significant improvement in patient care, both from a logistical/cost standpoint as well as from the perspective of maintaining appropriate and consistent glucose control. Risk factors prompting metformin witholding will be limited to patients with renal dysfunction (eGFR <45), known liver disease, significant alcohol abuse, or “acutely ill patients” (see below). FOR ALL OTHER PATIENTS, WITHOLDING METFORMIN IS UNNECESSARY.
Summary of our metformin policy:
Metformin is a medication used to treat non-insulin dependent diabetes mellitus. The most significant adverse effect of metformin therapy is the potential for the development of metformin-associated lactic acidosis. This condition is extremely rare, and seems to occur only when one or more contraindications for the drug are overlooked.
- All patients receiving intravascular iodinated contrast must be asked whether they are currently taking metformin-containing medications. Those who are on metformin-containing medications must be screened to determine whether they have risk factors for developing lactic acidosis.
THE FOLLOWING ARE RISK FACTORS FOR LACTIC ACIDOSIS:
a. Renal dysfunction (for our purposes, eGFR <45)
b. Liver dysfunction (for our purposes, any form of known liver disease)
c. Alcohol abuse (for our purposes, regular use of greater than 3 units per day)
d. Acutely ill patients*
- Patients with any of these risk factors for lactic acidosis must have their metformin-containing medications withheld for 48 hours after receiving contrast, and then restarted once renal function has been re-evaluated and found to be normal.
- Patients without risk factors for developing lactic acidosis do not need to discontinue metformin-containing medications, and do not need to have their renal function routinely re-evaluated.*The ACR Manual does not mention “acutely ill patients” but states that patients are at risk for lactic acidosis if they have “increased anaerobic metabolism,” i.e. patients with “cardiac failure, myocardial or peripheral muscle ischemia, sepsis, or severe infection.” For our purposes and for simplicity sake, we can consider anyone who is acutely ill to potentially be in a state of increased anaerobic metabolism and therefore at risk for lactic acidosis.