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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">Metformin is the main biguanide&#44; widely used in diabetes mellitus treatment&#46;<span class="elsevierStyleSup">1</span> It is a glycaemia-lowering agent<span class="elsevierStyleItalic"> </span>that promotes glucose entering the tissues and reduces hepatic gluconeogenesis and glucose synthesis&#46; It can reduce fasting and postprandial glycaemia and haemoglobin A<span class="elsevierStyleInf">1C</span> &#40;HbA<span class="elsevierStyleInf">1C</span>&#41;&#44; with weight loss and an improved lipid profile&#46;<span class="elsevierStyleSup">1</span> Studies such as the UKPDS also show that it reduces morbidity and mortality in patients with type 2 diabetes&#46;<span class="elsevierStyleSup">2</span> It is well absorbed through oral administration and it is mainly excreted through the kidney&#44; which is why it can accumulate in cases of renal function deterioration&#46; Its most frequent secondary effects are gastrointestinal&#44; such as diarrhoea&#44; abdominal pain and vomiting&#46; However&#44; a small percentage of patients may suffer a severe complication&#58; metformin-induced lactic acidosis&#44;<span class="elsevierStyleSup">3-5</span> especially subjects with comorbidities&#44; mainly liver&#44; heart and severe kidney diseases&#46; Therefore&#44; it is contraindicated in patients with chronic kidney disease&#46;</p><p class="elsevierStylePara">We describe 5 patients with severe metformin-induced lactic acidosis&#44; analysing the influence that kidney disease could have on its pathogenesis and evolution&#44; as well as the role that extrarenal depuration techniques can have on its treatment&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE REPORTS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 1</span></p><p class="elsevierStylePara">A 78-year-old woman with history of high blood pressure&#44; type 2 diabetes mellitus&#44; generalised osteoarthritis&#44; congestive heart failure &#40;class II on the New York Heart Association&#41; and chronic atrial fibrillation&#46; She was being treated with metformin &#40;850mg&#47;8hr&#41;&#44; glipizide &#40;5mg&#47;day&#41;&#44; lercanidipine &#40;10mg&#47;day&#41;&#44; lisinopril and hydrochlorothiazide &#40;20&#47;12&#46;5mg&#47;day&#41;&#44; acenocoumarol and occasionally ibuprofen&#46; Two days before being admitted she was taking ibuprofen &#40;600mg&#47;8hr&#41; due to bone pain&#46; Her general health started to deteriorate&#44; with vomiting and decreased level of consciousness&#46;</p><p class="elsevierStylePara">In the emergency department she was hypotensive&#44; poorly perfused&#44; and comatose &#40;Glasgow coma score 6&#47;15&#41;&#46; Analytical tests showed plasma creatinine&#58; 1&#46;79mg&#47;dl&#59; glycaemia&#58; 215mg&#47;dl&#59; and prothrombin activity&#58; 7&#37;&#46; The arterial blood gas test showed pH&#58; 7&#46;03&#59; bicarbonate&#58; 10mEq&#47;l&#59; and plasma lactic acid&#58; 14mmol&#47;l &#40;Table 1&#41;&#46; The chest X-ray revealed infiltration in the left base&#46;</p><p class="elsevierStylePara">She was transferred to the intensive care unit &#40;ICU&#41; and underwent orotracheal intubation with mechanical ventilation&#46; Vasoactive drugs and antibiotics were administered&#46; A lumbar puncture was performed&#44; and the result was compatible with pneumococcal meningitis&#46; Haemodialysis was performed with bicarbonate solution&#46; Her analytical tests then improved&#58; plasma creatinine &#40;Cr&#41;&#58; 1&#46;2mg&#47;dl&#59; and serum bicarbonate&#58; 22mEq&#47;l&#46; However&#44; the patient remained in a coma&#44; with low-voltage EEG&#46; She died 72 hours after being admitted&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 2</span></p><p class="elsevierStylePara">A 76-year-old woman with history of type 2 diabetes mellitus&#44; dyslipidaemia&#44; and depressive disorder&#46; She was being treated with metformin &#40;850mg&#47;8hr&#41;&#44; escitalopram &#40;20mg&#47;24hr&#41;&#44; mirtazapine &#40;30mg&#47;24hr&#41; and simvastatin &#40;40mg&#47;24hr&#41;&#46; In an analytical test taken 6 months before&#44; she had creatinine of 0&#46;81mg&#47;dl&#46;</p><p class="elsevierStylePara">Two weeks before being admitted she started treatment with ibuprofen &#40;600mg&#47;8hr&#41; for lower back pain&#46; A week before&#44; she had nausea&#44; with vomiting and diarrhoea&#44; which is why she went to the emergency department&#46; In the examination she had dry skin and mucosa and the analytical tests showed&#58; plasma Cr&#58; 9mg&#47;dl&#59; glucose&#58; 189mg&#47;dl&#59; urea&#58; 196mg&#47;dl&#59; haemoglobin&#58; 10&#46;9g&#47;dl&#59; sodium&#58; 125mEq&#47;l&#59; potassium&#58; 8&#46;6mEq&#47;l&#59; and lactic acid&#58; 6&#46;3mmol&#47;l&#46; The arterial blood gas test showed&#58; pH&#58; 7&#46;23&#59; and bicarbonate&#58; 15mEq&#47;l &#40;Table 1&#41;&#46; An abdominal ultrasound was performed showing bilateral ureterohydronephrosis secondary to bladder neoplasm&#46; Given that the patient was haemodynamically unstable&#44; haemodialysis was performed for 2 hours&#46; She then had&#58; Cr&#58; 5&#46;9mg&#47;dl&#59; potassium&#58; 6&#46;1mEq&#47;l&#59; pH&#58; 7&#46;39&#59; and bicarbonate&#58; 22mEq&#47;l&#46; Later&#44; a bilateral nephrostomy was performed with improved clinical symptoms and analytical values normalised&#58; Cr&#58; 1&#46;1mg&#47;dl&#44; pH&#58; 7&#46;31&#59; and bicarbonate&#58; 23mEq&#47;l&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 3</span></p><p class="elsevierStylePara">A 47-year-old man&#44; with long-standing type 2 diabetes&#44; being treated with metformin &#40;850mg&#47;8hr&#41; and glimepiride &#40;4mg&#47;day&#41;&#44; an active smoker and drinker&#46; He had had several episodes of acute non-<span class="elsevierStyleItalic">calculous </span>pancreatitis&#46; One week before he was admitted&#44; he showed signs of syncope while he was working in the field&#46; He then presented with intense asthenia&#44; hypoorexia&#44; general discomfort&#44; and postural hypotension&#46; He arrived at the health centre with blood pressure of 70&#47;35mm&#160;Hg and capillary glycaemia of 20mg&#47;dl&#44; and was subsequently administered IV glucagon&#46; Hypotension persisted in the emergency department&#44; with signs of extracellular volume depletion and tachypnoea&#46; Analytical tests showed&#58; plasma Cr&#58; 10&#46;3mg&#47;dl&#59; glycaemia&#58; 287mg&#47;dl&#59; and lactic acid&#58; 20mmol&#47;l&#46; The arterial blood gas test showed&#58; pH&#58; 6&#46;87 and bicarbonate&#58; 2&#46;2mEq&#47;l &#40;Table 1&#41;&#46; Orotracheal intubation was performed and he was admitted to the ICU with assisted ventilation and was administered inotropic agents&#46; He later underwent haemodialysis for four hours&#44; followed by continuous venovenous haemofiltration with improved analytical results&#46; Upon discharge he had Cr&#58; 1&#46;20mg&#47;dl&#59; pH&#58; 7&#46;46&#59; and bicarbonate&#58; 24&#46;6mEq&#47;l&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 4</span></p><p class="elsevierStylePara">A 65-year-old man&#44; with type 2 diabetes and history of revascularisation for ischaemic heart disease with mild systolic dysfunction and generalised atheromatosis&#46; He was being treated with enalapril &#40;40mg&#47;day&#41;&#44; atenolol &#40;50mg&#47;day&#41;&#44; acetylsalicylic acid &#40;300mg&#47;day&#41;&#44; fenofibrate &#40;200mg&#47;day&#41; and a fixed combination of rosiglitazone&#47;metformin &#40;2&#47;500mg&#47;12hr&#41;&#46; He was admitted to the emergency department due to acute deterioration of general health&#44; decreased consciousness&#44; and tachypnoea&#46; Five days before admission he had presented with epigastralgia associated with nausea&#44; vomiting and diarrhoea&#46; He continued his usual treatment&#46; The physical examination showed&#58; blood pressure&#58; 100&#47;60mm&#160;Hg&#44; oxygen saturation&#58; 84&#37; and auscultation found rales in the right lung base and abdominal vascular murmur&#46;</p><p class="elsevierStylePara">Analytical tests showed&#58; Cr&#58; 21&#46;4mg&#47;dl&#59; glucose&#58; 126mg&#47;dl&#59; potassium&#58; 6&#46;6mEq&#47;l&#59; creatine phosphokinase &#40;CPK&#41;&#58; 315 with normal troponin I&#59; and lactic acid&#58; 10&#46;2mmol&#47;l &#40;Table 1&#41;&#46; Furthermore&#44; leukocytes&#58; 16&#160;210&#47;&#181;l&#59; haemoglobin&#58; 13&#46;3g&#47;dl&#59; and platelets 407x1000&#47;&#181;l&#46; The chest X-ray showed condensation in the right base&#46; He was transferred to the ICU&#44; where he underwent orotracheal intubation&#44; mechanical ventilation and treatment with vasoactive drugs&#46; However&#44; he underwent cardiac arrest and needed CPR&#46; Treatment with continuous venovenous haemofiltration was started and maintained for five days with gradual improvement&#59; he was discharged from the ICU with plasma Cr&#58; 3&#46;5mg&#47;dl&#59; potassium&#58; 3&#46;3mEq&#47;l&#59; pH&#58; 7&#46;39&#59; and bicarbonate&#58; 20&#46;6mEq&#47;l&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case 5</span></p><p class="elsevierStylePara">An 87-year-old woman&#44; with history of high blood pressure and long-standing type 2 diabetes mellitus&#46; Furthermore&#44; she presented with chronic atrial fibrillation and severe pulmonary blood pressure &#40;for which she was being anticoagulated with acenocoumarol&#41; and polymyalgia rheumatica&#46; She was taking administered deflazacort &#40;6mg&#47;day&#41;&#44; metformin &#40;850mg&#47;8hr&#41;&#44; repaglinide &#40;2mg&#47;8hr&#41;&#44; candesartan&#47;hydrochlorothiazide &#40;16&#47;12&#46;5mg&#47;day&#41;&#44; omeprazole &#40;20mg&#47;day&#41;&#44; torasemide &#40;5mg&#47;day&#41; and nifedipine &#40;30mg&#47;day&#41;&#46; Three months before her plasma Cr was 1&#46;22mg&#47;dl&#46; She presented with significant diarrhoea&#44; vomiting and disorientation for two days before admission&#46; Capillary glycaemia was determined at 45mg&#47;dl&#46; In the emergency department she had blood pressure&#58; 101&#47;79mm&#160;Hg&#59; temperature&#58; 38&#186;C&#59; and oxygen saturation&#58; 98&#37;&#46; She presented with dry mucosa and slightly decreased consciousness with a Glasgow coma score of 13&#46;</p><p class="elsevierStylePara">Analytical tests showed&#58; Cr&#58; 8&#46;21mg&#47;dl&#59; glucose&#58; 262mg&#47;dl&#59; potassium&#58; 6&#46;2mEq&#47;l&#59; leukocytes&#58; 19&#160;220&#47;&#181;l&#59; haemoglobin&#58; 9&#46;9g&#47;dl&#59; and lactic acid&#58; 18mmol&#47;l&#46; Prothrombin activity was 12&#37;&#46; The arterial blood gas test showed&#58; pH&#58; 6&#46;6&#59; and bicarbonate&#58; 2&#46;6mEq&#47;l&#46; Given that admission to ICU was rejected due to associated comorbidities&#44; treatment with IV bicarbonate and inotropic agents were indicated&#44; but her health did not improve&#46; The patient died 10 hours after admission&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">Metformin is a glycaemia-lowering agent that is widely used to treat diabetic patients&#44; as a monotherapy or with associated anti-diabetic agents and even insulin&#46; Clinical practice guidelines especially recommend its use in obese type 2 diabetic patients and have even started to recommend it in subjects with an altered fasting blood glucose&#46;<span class="elsevierStyleSup">6&#44;7</span> Following oral administration&#44; peak metformin plasma levels are reached after 2&#46;5 hours&#46; Its protein binding is insignificant&#44; its distribution volume is high and it is mainly excreted by the kidney&#46; These characteristics promote drug elimination using extrarenal depuration techniques&#46;</p><p class="elsevierStylePara">Metformin&#8217;s main secondary effects are gastrointestinal &#40;anorexia&#44; nausea&#44; vomiting&#44; diarrhoea and abdominal pain&#41; and&#44; occasionally&#44; induces skin disorders or hypersensitivity reactions&#46;<span class="elsevierStyleSup">1</span> Metformin-induced lactic acidosis is a rare complication&#44; but it is potentially very severe and its incidence is estimated to be 3 cases per 100&#160;000 person-years&#46;<span class="elsevierStyleSup">8</span> Its cause is not well known&#44; although it seems to alter the mitochondrial oxidative metabolism on one hand&#44; and increase the intestinal lactic acid production and decrease intestinal glucose absorption&#46;<span class="elsevierStyleSup">9-11</span> However&#44; a recent systematic review of the Cochrane library concluded that there is no evidence showing that metformin is clearly associated with an increased risk of lactic acidosis&#46;<span class="elsevierStyleSup">12</span></p><p class="elsevierStylePara">The following predisposing factors to metformin-induced lactic acidosis development should be highlighted&#58; volume depletion&#44; renal function deterioration&#44; severe liver diseases&#44; congestive heart failure or use of drugs that interfere with renal autoregulation&#44; such as renin-angiotensin-aldosterone system inhibitors or non-steroidal anti-inflammatory drugs&#46;<span class="elsevierStyleSup">3</span> Among our patients&#44; two cases had volume depletion with acute renal failure&#44; three had taken renin-angiotensin-aldosterone system inhibitors and one received non-steroidal anti-inflammatory drugs&#46;</p><p class="elsevierStylePara">Mortality was related with a lower blood pH and higher plasma concentrations of lactic acid or metformin&#44;<span class="elsevierStyleSup">13</span> although other authors found a relationship with coagulation disorders&#46;<span class="elsevierStyleSup">5</span> Indeed&#44; in our study&#44; the two patients that died had significant coagulation disorders and the other patients made favourable progress&#44; having normal coagulation parameters&#46;</p><p class="elsevierStylePara">Initial treatment is based on haemodynamic and respiratory stability&#46; Furthermore&#44; the metabolic disorder must be corrected&#44; although using bicarbonate sodium is controvertial&#44;<span class="elsevierStyleSup">14</span> given that it could cause the haemoglobin disassociation curve to shift to the left&#44; a sodium overload&#44; and occasionally&#44; rebound metabolic alkalosis&#46;<span class="elsevierStyleSup">14&#44;15</span></p><p class="elsevierStylePara">For the most severe cases&#44; extrarenal depuration techniques have been used&#44; i&#46;e&#46; intermittent haemodialysis and continuous haemofiltration&#46;<span class="elsevierStyleSup">16 </span>Haemodialysis using a bicarbonate solution is the most rapid way to correct acidosis&#44; but continuous techniques should be considered for patients with haemodynamic instability&#46;<span class="elsevierStyleSup">9</span> A combination of the two techniques can also be used depending on the patient&#8217;s evolution&#46;<span class="elsevierStyleSup">17</span></p><p class="elsevierStylePara">The benefits of haemodialysis seem to be related to the correction of metabolic acidosis and drug elimination&#46; Prolonged sessions are recommended to increase clearance&#46;<span class="elsevierStyleSup">5&#44;15&#44;18</span></p><p class="elsevierStylePara">We performed haemodialysis on two patients&#44; one was treated with continuous haemodiafiltration and another one underwent both techniques&#46; Each technique was chosen in accordance with the haemodynamic stability of each patient&#59; continuous techniques were preferred for patients that presented with haemodynamic instability&#46; Despite treatment&#44; prognosis was poor for 40&#37; of our patients&#44; probably related to the severe associated diseases that they presented&#46;</p><p class="elsevierStylePara">To conclude&#44; diagnosis should be suspected in those subjects treated with the drug who present with severe lactic acidosis&#46; Special caution should be taken for patients with severe associated diseases such as liver or renal failure&#44; volume depletion or concomitant treatment with renin-angiotensin-aldosterone system inhibitors or non-steroidal anti-inflammatory drugs&#46;</p><p class="elsevierStylePara"><a href="grande&#47;10955&#95;108&#95;21671&#95;en&#95;t1&#95;10955&#46;jpg" class="elsevierStyleCrossRefs"><img src="10955_108_21671_en_t1_10955.jpg" alt="Clinical and analytical data&#44; and treatment received by patients"></img></a></p><p class="elsevierStylePara">Table 1&#46; Clinical and analytical data&#44; and treatment received by patients</p>"
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        "resumen" => "<p class="elsevierStylePara">La metformina es un f&#225;rmaco ampliamente utilizado en sujetos con diabetes mellitus y su eficacia para descender la glucemia y la hemoglobina&#160;A<span class="elsevierStyleInf">1C</span>&#160;&#40;HbA<span class="elsevierStyleInf">1C</span>&#41; es notable&#46; Sin embargo&#44; en algunos pacientes&#44; sobre todo en los que presentan&#160;comorbilidades&#44; puede provocar una acidosis l&#225;ctica grave que origina una elevada morbimortalidad&#46; El tratamiento de esta complicaci&#243;n se basa en la utilizaci&#243;n de medidas de soporte y&#44; en los casos m&#225;s graves&#44; en procedimientos de depuraci&#243;n extrarrenal&#44; como la hemodi&#225;lisis o la hemodiafiltraci&#243;n continua&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleItalic">Metformin is an antihyperglycemic agent commonly used in diabetic patients&#46; It is very effective and is able to reduce the plasma glucose and HbA<span class="elsevierStyleInf">1C</span>&#46; However&#44; in some patients&#44; specially those with comorbidities&#44; metformin can provoke severe lactic acidosis with high morbimortality&#46; Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures&#59; in severe cases&#44; procedures of extrarrenal purification like hemodialysis or continuous hemodiafiltration have been successfully used&#46;</span></p>"
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                  "referenciaCompleta" => "Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334(9):574-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8569826" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf 2010;33(9):727-40. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20701406" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Diabetes mellitus y riesgo cardiovascular. Recomendaciones del grupo de trabajo Diabetes Mellitus y Enfermedad Cardiovascular de la Sociedad Española de Diabetes 2009. Endocrinol Nutr 2010;57(5):220-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20444660" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Standards of medical care in diabetes-2010. Diabetes Care 2010;33(Suppl 1):S11-61. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20042772" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
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              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care 2008;31(11):2086-91. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18782901" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
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              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Bruijstens LA, Van Luin M, Buscher-Jungerhans PM, Bosch FH. Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment. Neth J Med 2008;66(5):185-90. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18490795" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
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                  ]
                ]
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            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Cusi K, Consoli A, DeFronzo RA. Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1996;81(11):4059-67. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8923861" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 2000;348(Pt 3):607-14. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10839993" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010(4):CD002967."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Dell'Aglio DM, Perino LJ, Kazzi Z, Abramson J, Schwartz MD, Morgan BW. Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Ann Emerg Med 2009;54(6):818-23. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19556031" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Teale KF, Devine A, Stewart H, Harper NJ. The management of metformin overdose. Anaesthesia 1998;53(7):698-701. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9771180" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ortega Carnicer J, Ambrós Checa A, Martín Rodríguez C, Ruiz Lorenzo F, Portilla Botelho M, Gómez Grande L. Sobredosis de metformina secundaria a insuficiencia renal aguda. A propósito de 6 observaciones. Med Intensiva 2007;31(9):521-5."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
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              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Lalau JD, Race JM. Lactic acidosis in metformin therapy. Drugs 1999;58(Suppl 1):55-60 [discussion 75-82]."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Panzer U, Kluge S, Kreymann G, Wolf G. Combination of intermittent haemodialysis and high-volume continuous haemofiltration for the treatment of severe metformin-induced lactic acidosis. Nephrol Dial Transplant 200419(8):2157-8."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
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              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Almirall J, Bricullé M, González-Clemente JM. Metformin-associated lactic acidosis in type 2 diabetes mellitus: incidence and presentation in common clinical practice. Nephrol Dial Transplant 2008;23(7):2436-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18388117" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
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