title: Metformin and antihypertensive therapy with drugs blocking the renin angiotensin system, a cause of concern?
abstract: BACKGROUND
  The burden of diabetes mellitus type 2 (DM2) is increasing worldwide. The combination of DM2 and hypertension (HT) is frequently encountered. Concurrent use of drugs blocking the renin angiotensin system (angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)) and metformin have become frequent in this group of patients. That combination can become life-threatening under certain circumstances.
  
  
  METHODS
  We present 5 patients with DM2 and HT who developed severe metformin-associated lactic acidosis in a setting with acute renal failure, precipitated by dehydration and aggravated by the use of ACEI or ARB.
  
  
  RESULTS
  None of the patients had reduced renal function before the acute illness. They were admitted to the hospital in critical condition with severe metabolic acidosis (pH 6.60 6.94), high S-lactate (14 - 23 mmol/l) and S-creatinine 796 1,621 micromol/l. They were all hypothermic and 3 were hypoglycemic. All developed circulatory and respiratory collapse. They were treated with either intermittent bicarbonate hemodialysis (HD) or with continuous venovenous hemodiafiltration (CVVHDF) and bicarbonate buffering. All patients recovered without renal sequela.
  
  
  CONCLUSIONS
  We believe that the incidence of metformin-associated lactic acidosis in Norway may become more frequent due to increased use of metformin and drugs blocking the renin angiotensin system. The awareness of lactic acidosis as a complication to the use ofmetformin in predisposed individuals is important. General advice should be given to patients regarding reduction of dosage or withdrawal of the drugs during acute intercurrent illness with dehydration. Early diagnosis and treatment of metformin-associated lactic acidosis are crucial for the patient outcome. Hemodialysis can be life-saving and should be started without delay.
authors.affiliation: Department of Nephrology, Ulleval University Hospital, Oslo, Norway. helga.gudmundsdottir@ulleval.no
authors.forename: H
authors.initials: H
authors.lastname: Gudmundsdottir
authors.forename: H
authors.initials: H
authors.lastname: Aksnes
authors.forename: K
authors.initials: K
authors.lastname: Heldal
authors.forename: A
authors.initials: A
authors.lastname: Krogh
authors.forename: S
authors.initials: S
authors.lastname: Froyshov
authors.forename: N
authors.initials: N
authors.lastname: Rudberg
authors.forename: I
authors.initials: I
authors.lastname: Os
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced*; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000009:adverse effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D008687:Metformin