Case Report

Transient Vision loss in a patient with metformin-associated lactic acidosis^?

Abstract

Metformin-associated lactic acidosis (MALA) can occur when renal function is impaired and metformin accumulates in the body. Symptoms of MALA are varied and have rarely included vision loss. The objective of the study was to describe a case of MALA-associated vision loss. A 67-year- old woman presented to an emergency department (ED) with a complaint of acute vision loss. She was taking metformin for treatment of type 2 diabetes mellitus. In the ED, the patient had a temperature of 32.3?C (90.1?F), a heart rate of 55 beats per minute, a blood pressure of 117/94 mmHg, and respiratory rate of 34 breaths per minute, with a Pulse oximeter reading of 98% on room air. On neurologic examination, she was awake and alert and was answering questions. She had no visual acuity, visual fields were not intact, her fundoscopic examination result was unremarkable, and her pupils were midsized and slow to react. Laboratory evaluation revealed a severe lactic acidosis (pH 6.65; lactate, 19.9 mmol/L). Creatinine concentration was 7.0 mg/dL (baseline creatinine, 1.3 mg/dL). Her metformin concentra- tion was 28 ug/mL. Methanol and formic acid concentrations were negative. Result of her head computed tomographic scan was unremarkable. She underwent dialysis and had resolution of her metabolic acidosis with full return of her vision. This patient experienced transient vision loss associated with severe acidosis due to metformin. Treatment of the acidosis was effective in restoring vision in this patient.

Metformin, a biguanide oral antihyperglycemic, was approved for use in the United States in 1992 for treatment of type 2 diabetes mellitus. Since its introduction, metfor- min-associated lactic acidosis (MALA) has become a well- recognized adverse event. This case describes the occurrence of MALA-associated vision loss.

A 67-year-old woman presented to the emergency department (ED) complaining of acute painless bilateral vision loss. The patient’s vision loss occurred over the course

^? This work was presented in abstract form at the North American Congress of Clinical Toxicology in September 2009.

of 1 hour previously in the afternoon. She was transported by ambulance to the hospital.

The patient’s medical history was significant for coronary artery disease, peripheral vascular disease, hypertension, type 2 diabetes mellitus, hypercholesterolemia, and osteoar- thritis. She reported rare ethanol use and denied tobacco or illicit drug use. Her medication list included metformin, lisinopril, aspirin, metoprolol, clopidogrel, and acetamino- phen/hydrocodone. Her review of systems was negative for trauma, headache, eye pain, focal weakness or numbness, weight change, recent illness, overdose of any medication, or ingestion of xenobiotics other than her prescribed medications. On presentation, her rectal temperature was 32.3?C (90.1?F), heart rate was 55 beats per minute, blood pressure was 117/94 m mHg, respiratory rate was 34 breaths per minute, and pulse oximeter reading was 98% on room air. The patient was lying calmly supine on the stretcher under bright lights with her eyes opened, and she answered questions slowly in 1- or 2-word answers. She had no signs of trauma on her head or body. Her pupils were midsized, equal, and slow to react. Visual acuity and fields were not intact. Fundoscopic examination did not reveal abnormali- ties. She was awake and oriented to person, place, and time. The patient followed simple commands but was unable to comply with a full cranial nerve examination. Strength was intact to resistance against gravity alone, and sensation was

intact to fine touch. Deep tendon reflexes were absent.

Laboratory findings are displayed in Table 1, and other relevant clinical data are listed in Table 2. Her baseline creatinine was 1. 3 mg/dL from 3 months prior.

Emergency department management included treatment of her hyperkalemia with Calcium gluconate, insulin, and glucose. She also received 3 boluses of sodium bicarbonate, but her metabolic acidosis and vision loss persisted. She was administered fomepizole for possible methanol intoxication, and Emergent hemodialysis was initiated. After dialysis,

10 hours after her presentation to the ED, the patient reported return of vision. Her visual acuity was 20/ 30 bilaterally. Her pH had increased to 7.48, her hypothermia had resolved, and her succeeding neurologic examination revealed no deficits. The patient’s laboratory abnormalities were also corrected (Table 1). Upon discharge, her use of metformin was discontinued.

This patient’s metabolic acidosis resulted from long-term metformin use in the setting of an elevated creatinine, which

0735-6757/$ – see front matter (C) 2010

1059.e6 Case Report

Table 1 Laboratory values during patient’s hospitalization

returned to near normal. Both Feeney et al [7] and Yanagawa et al [8] described patients with alcoholic ketoacidosis both of whom had a pH less than 6.80 and acute vision loss. Both patients’ vision improved with treatment of their acidosis. Neuroimaging for both was noncontributory.

Our patient presented similarly to these cases with a pH less than 7.0, acute onset of total vision loss, unremarkable neuroimaging, negative methanol and formic acid levels, and resolution of her vision loss after treatment of her acidosis. Based on the clinical similarities and successful clinical outcomes of patients documented in these previous case reports, we attributed this patient’s vision loss to MALA.

Animal studies suggest that retinal cell function may be pH dependent. Fish and tiger salamander retinal horizontal cells’ response to light is pH sensitive [9,10], and mammalian retinal cell function becomes disrupted at a pH of less than

7.0 [11]. These effects may extend to humans and may serve as an explanation for acidosis-associated vision loss.

This case report describes a rarely reported association between transient acute vision loss and MALA. definitive treatment of the acidosis appears to facilitate the resolution of vision loss. The etiology of this association is not fully

ultimately caused decreased excretion of the drug [1-3]. Her presenting complaint was vision loss. Biguanide-associated vision loss has infrequently been reported. In 1977, Sorenson

[4] documented a case of reversible vision loss in a patient who ingested ethanol and phenethylbiguanide. The patient had a lactic acidosis with visual acuity intact to light perception only. The patient’s visual acuity returned to baseline after treatment with sodium bicarbonate, insulin, and glucose. In 2003, Chu et al [5] reported a case of MALA- associated vision loss in which the patient had a pH of 6.64 and no visual acuity. Neuroimaging result was unremark- able. Visual acuity improved after treatment with dialysis and resolution of acidosis.

Vision loss resulting from metabolic acidosis has been described in other clinical scenarios. In 1981, Deutsch [6] reported a case of a man with severe diabetic ketoacidosis who presented with acute total vision loss and a pH of 6.89. After treatment with insulin and sodium bicarbonate, his vision

Table 2 Other laboratory and radiographic results Toxicology

Ethanol, 0

Methanol, 0

Formic acid, 0

propylene glycol level, 2.3 mg/dL Ethylene glycol, 0

Metformin, 28 ug/mL (therapeutic range, 1-2 ug/mL) Carboxyhemoglobin, 0.2%

Salicylates, b1 mg/dL Acetaminophen, 14.6 ug/mL Radiographic findings

Head computed tomographic scan: no acute changes

understood. Additional study in humans to further under- stand the mechanisms underlying this relationship would be of interest.

Allyson A. Kreshak MD Division of Medical Toxicology Department of Emergency Medicine

University of California San Diego Medical Center

San Diego, CA 92103, USA California Poison Control System

San Diego Division San Diego, CA 92103, USA

Veterans’ Administration Medical Center

La Jolla, California San Diego, CA 92103, USA

Richard F. Clark MD Division of Medical Toxicology Department of Emergency Medicine

University of California San Diego Medical Center

San Diego, CA 92103, USA California Poison Control System

San Diego Division San Diego, CA 92103, USA

doi:10.1016/j.ajem.2010.01.024

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3. Peters N, Jay N, Barraud D, et al. Metformin-associated lactic acidosis in an intensive care unit. Crit Care 2008;12(6):R149 Epub 2008 Nov 26.

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