Mechanism of action of metformin:
Metformin is a biguanide drug widely used to control hyperglycemia in type 2 diabetes melitus.
The proposed mechanism of action of metformin is: to reduce liver gluconeogenesis enhancing peripheral glucose production uptake,
as a result of increased sensitivity of peripheral tissues to insulin.
Metformin is excreted unchanged by the kidneys.
The renal route eliminates 90% of the absorbed drug within the first 24 hours.
Metformin seems to cause increased lactic acid production by the intestines.
Any factors that decrease metformin excretion or increase blood lactate level are important risk factors for lactic acidosis.
The literature reviews the relationship between metformin administration and the use of iodinated contrast medium and the risk of lactic acidosis.
There is no interaction between metformin and iodinated contrast medium.
Metformin itself is not a nephrotoxic drug.
Iodinated X-ray contrast media are not independent risk factor for patient taking metformin but are a concern only in the presence of underlying renal dysfunction (Fig. 3).
Factors that depress the ability to metabolize lactate are contraindications to the use of metformin ( Fig. 4 ).
Several guidelines developed by radiological organizations address precautions for administration of iodinated contrast medium to patients who are taking metformin.
There are differences in their recommendations and the scientific evidence on which are based.
The guidelines reviewed are:
-American College of Radiology (ACR)
-Royal Australian and New Zealand College of Radiologists (RANZCR)
-Royal College of Radiologist (RCR)
-Canadian Association of Radiologists (CAR)
-European Society of Urogenital Radiology (ESUR)
-Spanish agency of the medicament
These guidelines are inconsistent and unclear in their recommendations about the following critical issues like as ( Fig. 5 and Fig. 6):
- The level at which renal function is considered abnormal
- How recent the renal function test result should be
- Whether metformin administration should be stopped at all at the time of contrast medium injection in patients with normal renal function
- When metformin should be stopped if renal function is abnormal
- Whether it is necessary to retest renal function in patients with normal baseline function before restarting metformin administration
- What level of renal function is necessary before resumption of metformin administration if renal function is retested
Description of the diagnostic procedure to be followed in our hospital:
We review the guidelines and protocol of various scientific societies to establish a protocol to manage patients treated with metformin who are going to administer intravenous contrast.
In our radiology department developed a diagnostic procedure to manage these patients following the recommendations of The Spanish Agency for Medicines and Health Products,
developed by the Ministry of Health and Social Policy with metformin ( Fig. 7 ):
Metformin should be discontinued before or at the time of iodinated contrast administered intravascular via and not reinstituted until 48 hours afterwards and following an assessment of renal function and found to be normal.
This procedure requires the involvement of: requesting physician ( Fig. 8),
the nursing staff of our service ( Fig. 9 and Fig. 10),
the radiologist,
and finally the doctors and nurses of Primary Care ( Fig. 11).
Before performing the exploration with intravenous contrast,
the nurse staff of our department review: requests for exploration,
the creatinine and serum urea and metformin intake,
as well as the history of allergies or other risk factors for nephrotoxicity.
When our staff calling the patient to indicate the date of exploration,
we indicate the temporary suspension of metformin treatment and indicate stop taking metformin at the exam day.
The day of examination the nurse explains the procedure to the patient,
the risk of possible pharmacologic interaction between metformin and iodinated contrast,
and the temporary suspension of medication and subsequent reintroduction by Primay Care Doctor.
Also delivers information documents like as,
the application of the analytic of renal function directed at primary care doctor for 48 hours after contrast administration,
furthermore the appointment request with your primary doctor the day after the blood analytical.
After the examination,
blood extraction is performed in each health center coordinated with the Hospital Radiology Department.
Primary care physician will be responsible for introducing metformin treatment when renal function is within normal ranges.
( Fig. 12 and Fig. 13)
Material and methods:
The health area of Tudela covers a population of approximately 100,000 people,
which 2840 people are taking metformin. On the other hand,
7767 computerized axial tomography and 184 intravenous urography were performed in 2011.
We retrospective review the studies performed in our hospital with intravenous contrast in 2011: 3871 studies were performed,
of which 3687 were CT and 184 were urographies.
Moreover,
198 patients were taking metformin,
but 37 were excluded because they did not perform the analytical control to assess renal function at 48 hours after administration of contrast.
Finally this study included 161 patients.
We analyzed creatinine values in patients who were taking metformin and who had been made a scan with IV contrast.
Analyses were carried out based on various factors such as age,
sex,
time between the test and analytical renal function and initial creatinine levels and after contrast examination.
We excluded patients in whom the delay between the analytical and the contrast test was over 7 days.
To measure kidney function we used the serum creatinine level,
with normal baseline values < 1.5 mg/dL.
Antiquity of renal function test was established in a period of one year prior to the administration of iodinated contrast.
Statistical analysis was performed with the program G-Stat 2.0