Systematic Review of Current Guidelines, and Their Evidence Base, on Risk of Lactic Acidosis after Administration of Contrast Medium for Patients Receiving Metformin

Published Online:https://doi.org/10.1148/radiol.09090690

Current recommendations about the need to cease metformin administration and retest kidney function after iodinated contrast medium administration in patients who are taking metformin lack an evidence base, and the recommendations vary greatly among international radiological professional organizations.

Purpose

To systematically review evidence about the relationship between metformin administration and the use of iodinated contrast medium and risk of lactic acidosis (LA) and to assess the quality of five current guidelines for use of contrast medium in patients who are taking metformin.

Materials and Methods

A search strategy was developed by using search termsrelated to metformin, contrast media, and LA. Searches were conducted in MEDLINE (Ovid), all Evidence-based Medicine Reviews (Ovid), EMBASE, and Cochrane library databases and were augmented with searches for evidence-based guidelines on radiology and evidence-based medicine Web sites by using the Google Internet search engine. Guidelines were appraised by two independent reviewers by using the Appraisal of Guidelines Research and Evaluation Collaboration Instrument. Other studies were appraised by using structured appraisal checklists.

Results

Five guidelines were identified and five empirical studies met inclusion criteria. All guidelines had poor scores on some Appraisal of Guidelines for Research and Evaluation (AGREE) Collaboration criteria; poorer scores tended to occur in relation to objective assessment of rigor of guideline development, editorial independence, and applicability of the guideline to clinical practice. Lack of agreement was observed among guidelines about the need to stop taking metformin after contrast medium is administered, risk of LA in patients with normal renal function before contrast medium injection, recommended method of measuring renal function, and values used to define abnormal function. The evidence that was used as a basis for determining the guidelines for metformin administration, use of contrast medium, and risk of LA consisted of a limited number of observational studies, including case reports, summaries of case reports, and case series (National Health and Medical Research Council of Australia level IV–V evidence). More important, it was not apparent that a systematic search strategy had been used to identify the studies referenced by the guidelines nor that the referenced studies had been appraised. Individual guideline recommendations were not clearly connected to cited references.

Conclusion

Substantial inconsistencies exist between the recommendations of the five international guidelines about contrast medium administration in patients who are taking metformin. These are, in part, caused by the low level of evidence underpinning guideline recommendations.

© RSNA, 2010

Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090690/-/DC1

References

  • 1 Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574–579. Crossref, MedlineGoogle Scholar
  • 2 Lada P, Idrees U. Toxicity of oral agents used to treat diabetes. J Pharm Pract 2005;18(3):145–156. CrossrefGoogle Scholar
  • 3 Parra D, Legreid AM, Beckey NP, Reyes S. Metformin monitoring and change in serum creatinine levels in patients undergoing radiologic procedures involving administration of intravenous contrast media. Pharmacotherapy 2004;24(8):987–993. Crossref, MedlineGoogle Scholar
  • 4 Hermann LS, Melander AIn: Alberti KGMM, DeFronzo RA, Keen H, Zimmet P, eds. Text-book of diabetes mellitus. New York, NY: Wiley, 1992; 773–795. Google Scholar
  • 5 Quader MA, Sawmiller C, Sumpio BA. Contrast-induced nephropathy: review of incidence and pathophysiology. Ann Vasc Surg 1998;12(6):612–620. Crossref, MedlineGoogle Scholar
  • 6 Lalau JD, Lacroix C, Compagnon Pet al.. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995;18(6):779–784. Crossref, MedlineGoogle Scholar
  • 7 Salpeter S, Greyber E, Pasternak G, Salpeter E. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database of Systematic Reviews, 2006. No. CD002967. http://www.cochrane.org/reviews/. Published online January 25, 2006. Accessed March 2009. Google Scholar
  • 8 Salpeter S, Greyber E, Pasternak G, Salpeter E. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database of Systematic Reviews, 2002. No. CD002967. http://www.cochrane.org/reviews/. Published online February 27, 2002. Accessed March 2009. Google Scholar
  • 9 The AGREE Collaboration. Appraisal of Guidelines for Research & Evaluation. AGREE Instrument. http://www.agreecollaboration.org. Published September 2001. Accessed March 2009. Google Scholar
  • 10 American College of Radiology. Manual on contrast media, version 6 http://www.acr.org/SecondaryMainMenuCategories/quality_safety/contrast_manual.aspx. Published 2008. Accessed March 2009. Google Scholar
  • 11 Royal Australian and New Zealand College of Radiologists. Guidelines for metformin hydrochloride and intravascular contrast media. http://www.ranzcr.edu.au/collegegroups/reference/EBM/mhicm_guidelines.cfm. Published 2003. Accessed March 2009. Google Scholar
  • 12 Royal College of Radiologists. Standards for iodinated intravascular contrast agent administration to adult patients. http://www.rcr.ac.uk/docs/radiology/pdf/IVcontrastPrintFinal.pdf. Published 2005. Accessed March 2009. Google Scholar
  • 13 Canadian Association of Radiologists. Consensus guidelines for the prevention of contrast induced nephropathy. http://www.carj.ca/issues/2007-Apr/79/79.pdf. Published 2007. Accessed March 2009. Google Scholar
  • 14 European Society of Urogenital Radiologists. ESUR guidelines on contrast media. http://www.esur.org/fileadmin/Guidelines/ESUR_2007_Guideline_6_Kern_Ubersicht.pdf. Published 2007. Accessed March 2009. Google Scholar
  • 15 Thomsen HS, Morcos SK. Contrast media and metformin: guidelines to diminish the risk of lactic acidosis in non-insulin-dependent diabetics after administration of contrast media. ESUR Contrast Media Safety Committee. Eur Radiol 1999;9:738–740. Crossref, MedlineGoogle Scholar
  • 16 Jackson N. Metformin associated lactic acidosis following administration of intravenous contrast media. Centre for Clinical Effectiveness Evidence Centre Evidence report, 2002. Health Technology Assessment (HTA) database. York, England: Centre for Reviews and Dissemination, University of York, 2002. www.crd.york.ac.uk. Published August 11, 2003. Accessed March 2009. Google Scholar
  • 17 McCartney MM, Gilbert FJ, Murchison LE, Pearson D, McHardy K, Murray SD. Metformin and contrast media: a dangerous combination?. Clin Radiol 1999;54:29–33. Crossref, MedlineGoogle Scholar
  • 18 Nawaz S, Cleveland T, Gaines PA, Chan P. Clinical risk associated with contrast angiography in metformin treated patients: a clinical review. Clin Radiol 1998;53:342–344. Crossref, MedlineGoogle Scholar
  • 19 Millican S, Cottrell N, Green B. Do risk factors for lactic acidosis influence dosing of metformin? J Clin Pharm Ther 2004;29:449–454. Crossref, MedlineGoogle Scholar
  • 20 Chan NN, Brain HPS, Feher MD. Metformin-associated lactic acidosis: a rare or very rare clinical entity?. Diabet Med 1999;16:273–281. Crossref, MedlineGoogle Scholar
  • 21 Lalau JD, Race JM. Lactic acidosis in metformin therapy: searching for a link with metformin in reports of ‘metformin-associated lactic acidosis.’ Diabetes Obes Metab 2001;3:195–201. Crossref, MedlineGoogle Scholar
  • 22 Calabrese AT, Coley KC, DaPos SV, Swanson D, Rao RH. Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy.. Arch Intern Med 2002;162(4): 434–437. Crossref, MedlineGoogle Scholar
  • 23 Jain V, Sharma D, Prabhakar H, Dash HH. Metformin-associated lactic acidosis following contrast media-induced nephrotoxicity. Eur J Anaesthesiol 2008;25(2):166–167. Crossref, MedlineGoogle Scholar
  • 24 Stades AM, Heikens JT, Erkelens DW, Holleman F, Hoekstra JBL. Metformin and lactic acidosis: cause or coincidence? a review of case reports. J Intern Med 2004;255:179–187. Crossref, MedlineGoogle Scholar
  • 25 Gruberg L, Mintz GS, Mehran Ret al.. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol 2000;36(5):1542–1548. Crossref, MedlineGoogle Scholar
  • 26 Bashore TM, Bates ER, Berger PBet al.. American College of Cardiology/Society for Cardiac Angiography and Interventions Clinical Expert Consensus Document on cardiac catheterization laboratory standards: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001;37(8):2170–2214. http://www.acc.org/qualityandscience/clinical/consensus/angiography/angiography_ref.htm. Published 2001. Accessed March 2009. Google Scholar
  • 27 Heupler FA. Guidelines for performing angiography in patients taking metformin. Members of the Laboratory Performance Standards Committee of the Society for Cardiac Angiography and Interventions [editorial]. Cathet Cardiovasc Diagn 1998;43:121–123. Crossref, MedlineGoogle Scholar
  • 28 Prinseau J, Jardin F, Sanchez Aet al.. Acute renal failure after intravenous urography in diabetics: incidence of lactic acidosis in metformin treatment [in French]. Ann Med Interne (Paris) 1977;128(2):173–177. MedlineGoogle Scholar

Article History

Received, April 21, 2009; revision requested, June 3; final revision received, June 19; accepted, July 1; final version accepted, July 15.
Published online: Dec 8 2009
Published in print: Jan 2010