Case Report
Development of Acute Metabolic Acidosis in a Pediatric Patient with Idiopathic Intracranial Hypertension Treated with Acetazolamide: A Case Report
Mitchell Strohmaier1, Regan A Baum2*, Abby M Bailey2 and Jonathan Bronner2
1Department of Emergency Medicine, St. Elizabeth Healthcare, USA
2Department of Emergency Medicine, University of Kentucky Health Care, USA
*Corresponding author: Regan A Baum, Department of Emergency Medicine, University of Kentucky Health Care 800 Rose Street, H110 Lexington, KY, USA
Published: 30 Jun, 2018
Cite this article as: Strohmaier M, Baum RA, Bailey AM,
Bronner J. Development of Acute
Metabolic Acidosis in a Pediatric Patient
with Idiopathic Intracranial Hypertension
Treated with Acetazolamide: A Case
Report. Ann Clin Case Rep. 2018; 3:
1530.
Abstract
Background: Idiopathic intracranial hypertension (IIH) treatment consists of both lifestyle
modification and medical/surgical therapy. Acetazolamide, a carbonic anhydrase inhibitor, is
the primary medical treatment with adverse effects including neurologic symptoms and the
development of metabolic acidosis.
Case Presentation: We present a case report of a pediatric patient (with pre-diabetes treated with
metformin) who acutely developed metabolic acidosis and paresthesias following treatment with
acetazolamide for IIH diagnosis.
Conclusion: Special awareness by the clinician must be undertaken when acetazolamide is initiated
in the presence of current treatment with additional medications that could contribute to the
furthering of metabolic acidosis.
Keywords: Metabolic acidosis; Acetazolamide; Idiopathic intracranial hypertension; Metformin
Introduction
Idiopathic intracranial hypertension (IIH; formerly pseudo tumor cerebri) is a disorder involving the elevation of intracranial pressure. IIH is a disease seen more commonly amongst women, particularly obese women, of childbearing age [1]. The treatment of IIH involves modification of lifestyle factors (such as lowering sodium intake or reducing body weight), eliminating potential causal factors (such as discontinuing tetracyclines or vitamin A therapies), followed by medical/ surgical therapy. Acetazolamide has been used effectively to lower intracranial pressures by reducing production of cerebrospinal fluid (CSF). This is done via inhibition of carbonic anhydrase in the choroid plexus [2]. While this treatment has become one of the mainstays of medical therapy for IIH, it is not without risk. Recent randomized, controlled clinical trials have demonstrated that the odds of developing paresthesias, nausea/vomiting, fatigue, and dysgeusia were higher with acetazolamide compared with placebo [3]. Additionally, the development of metabolic acidosis in patients treated with acetazolamide has been evidenced and diagrammed previously in patients with renal insufficiency [4]. We report a case of a pediatric patient, on treatment for prediabetes with metformin, displaying normal renal function who developed paresthesias and metabolic acidosis following treatment of IIH with acetazolamide.
Case Report
A 14-year-old obese female with a past medical history significant for prediabetes treated with metformin presented to the emergency department (ED) secondary to a chief complaint of intermittent bifrontal and occipital headaches that lasted for hours at a time. The patient had presented previously to the emergency department for similar symptoms where imaging and laboratory studies were performed and reported to have been normal. Given ongoing symptoms, the patient and family decided to seek additional evaluation. At the time of this evaluation in the ED, the patient denied any neurologic complaints including numbness, weakness, and paresthesias. The patient was given analgesic medication for treatment of headache. Given patient’s age, gender, and weight there was concern for IIH. A lumbar puncture was performed and opening pressure was found to be 30cm of H2O. Following drainage of CSF, acetazolamide therapy was initiated at a dose of 500 mg orally twice daily. The patient was discharged from the ED to follow up with a pediatric neurologic specialist. Two days following the patient’s above evaluation in the ED, the patient re-presented with complaint of a two-day history of paresthesias localizing to the bilateral lower extremities as well as facial swelling. The patient and family noted that symptoms began following a total of three prescribed doses of acetazolamide. Laboratory evaluation (Table 1) in the ED demonstrated decreased plasma bicarbonate concentration 12 mmol/L (normal range 21 mmol/L to 29 mmol/L). Given diminished plasma bicarbonate concentration, a venous blood gas (VBG) was drawn. VBG demonstrated pH of 7.30, base deficit of 10.6 and bicarbonate of 15. Anion gap was found to be elevated at 17. Given the patient’s concomitant treatment with metformin, a serum lactate concentration was drawn to assess for signs of lactic acidosis. Lactate was found to be normal at 1.0 mmol/L. The patient was admitted to the hospital with signs concerning for an anion gap metabolic acidosis with appropriate respiratory compensation and superimposed non-gap metabolic acidosis. The patient was admitted to a general pediatrics service, monitored and given intravenous fluids. Metformin and acetazolamide were discontinued. Repeat laboratory studies following admission demonstrated normalization of anion gap and improvement in plasma bicarbonate concentration. Presenting symptoms also improved following admission and discontinuation of pharmacotherapies. The patient was discharged on hospital day 2.
Table 1
Discussion
There is minimal information in the literature describing drugdrug
interactions between acetazolamide and metformin resulting
in acidosis. Acetazolamide is a carbonic anhydrase enzyme inhibitor
most commonly used for treatment of altitude sickness, glaucoma
and other indications where decreasing the formation of CSF would
be advantageous [5]. Its mechanism of action is likely multifactorial
and most commonly attributed to the inhibition of the carbonic
anhydrase enzyme leads to decreases in CSF and aqueous humor
of the eye resulting in decreases in ICP and intraocular pressure.
Acetazolamide is known to alter the taste of foods, decreasing caloric
consumption, thus resulting in weight loss [2]. A diuretic action
occurs when acetazolamide increases the excretion of bicarbonate
in the renal tubule leading to sodium, potassium, and water losses.
This action is believed to be the cause of hyperchloremic metabolic
acidosis [5,6]. Acidosis has been more commonly reported in patients
with underlying renal insufficiency, elderly populations or in those
with diabetes who are concomitantly treated with acetazolamide [5].
Metformin is an oral antidiabetic medication commonly used
in the treatment of noninsulin-dependent diabetes. Metformin
decreases glucose absorption from the gastrointestinal tract, hepatic
production of glucose, increases peripheral glucose utilization and
is exclusively eliminated by the kidneys [7]. The manner in which
metformin precipitates lactic acidosis is controversial and multiple
different mechanisms have been proposed. The first is related to
increased drug plasma levels due to renal injury or dehydration and
second involves alterations in mitochondrial respiration [8,9].
The patient in this case report did not have a lactic acidosis as
is typical of metformin accumulation due to dehydration. The
diuretic action of the acetazolamide likely resulted in dehydration
thus transiently increasing metformin plasma levels adding to the
hyperchloremic acidosis that was potentially occurring from the
acetazolamide.
To evaluate the likelihood of this patient presentation being
the result of a medication adverse event application of the Naranjo
Adverse Drug Reaction Scale Probability Scale was applied. Based
on the application of this scale the patient case described above is
categorized as possible as it appeared after the acetazolamide was
initiated, improved upon discontinuation and other potential causes
of the disease state and patient specific factors were not identified
[10].
Conclusion
The treatment of IIH with the carbonic anhydrase inhibitor acetazolamide is well documented in medical literature, although uncommonly seen by most in clinical practice. The case presented catalogues the development of acute metabolic acidosis in a pediatric patient concomitantly treated with metformin, which has been known to result in the development of acidosis. The medical provider must be aware that adverse events can develop in the pediatric patient treated with acetazolamide. Providers must also consider the impact that concomitant therapies like metformin could have on developing more serious adverse events such as metabolic acidosis.
References
- Jensen RH, Radojicic A, Yri H. The diagnosis and management of idiopathic intracranial hypertension and the associated headache. Ther Adv Neurol Disord. 2016;9(4):317-26.
- Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010; 28(3):593-617.
- ten Hove MW, Friedman DI, Patel AD, Irrcher I, Wall M, McDermott MP, et al. Safety and Tolerability of Acetazolamide in the Idiopathic Intracranial Hypertension Treatment Trial. J Neuroophthalmol. 2016; 36(1):13-9.
- Maisey DN, Brown RD. Acetazolamide and symptomatic metabolic acidosis in mild renal failure. Br Med J (Clin Res Ed). 1981; 283(6305):1527-8.
- Venkatesha SL, Umamaheswara Rao GS. Metabolic acidosis and hyperventilation induced by acetazolamide in patients with central nervous system pathology. Anesthesiology. 2000; 93(6):1546-8.
- Acetazolamide. Sagent Pharmaceuticals, Schaumburg, IL; 2013.
- Glucophage (metformin hydrochloride). Bristol-Myers Squibb Company, Princeton, NJ; 2017.
- DeFronzo, R., et al., Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism, 2016. 65(2): p. 20-9.
- Visconti, L., et al., Metformin-related lactic acidosis: is it a myth or an underestimated reality? Ren Fail, 2016. 38(9): p. 1560-1565.
- Naranjo, C, etal., A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30(2):239-45.