Anion gap metabolic acidosis in”>Case Report

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American Journal of Emergency Medicine

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Negative anion gap metabolic acidosis in salicylate overdose-a zebra!?,??

Abstract

Salicylate poisoning classically results in an increased anion gap metabolic acidosis. We discuss a case of normal anion gap metabolic acidosis despite elevated serum salicylate concentration. This Diagnostic dilemma stemmed from aberrant reading of salicylate ions by analyzer electrodes as Chloride ions leading to falsely negative anion gap. On review, this phenomenon is found to be possible with a number of commonly used analyzers. In emergency department settings, high level of clinical suspicion for salicylate poisoning should be maintained, and metabolic acidosis with normal anion gap should not be used to rule out salicylate overdose. This can prevent significant avoidable morbid- ity and mortality.

Poisoning with salicylate-containing products is one of the common causes of emergency department (ED) visits due to drug overdose, mainly due to wide availability and easy access. In 2007, more than 4800 exposures to aspirin alone were reported including 63 deaths. Classically, the diagnosis of Salicylate toxicity is based on the clinical presentation, presence of an anion gap acidosis, and an elevated serum salicylate concentration [1]. Patients commonly present with nausea and vomiting, abdominal pain, lethargy, tinnitus, dizziness, seizures, or cerebral edema depending on the dose consumed. The most common cause of death is cardiopulmonary arrest due to pulmonary edema, seen in the most Severe forms of salicylate poisoning.

A 30-year-old man presented to the ED and the emergency medical services reported possibility of alcohol ingestion and overdose of prescription Keppra. The patient was sweating profusely and required Ativan and Haldol to decrease his agitation. He was tachycardic, tachypneic, and had dry mucous membranes. His neurologic examination was significant for confusion and aggressive behavior. Remainder of the systemic examination was normal.

The initial workup was significant for sodium 146 mEq/L, chloride 118 mEq/L, CO₂ 21 mEq/L, serum urea nitrogen 12 mg/dL, creatinine 1.0 mg/dL, anion gap 7, white blood cell count 14400 cells/mm³, hemoglobin level 15.8 mg/dL, platelets 205 thousand cells/mm³, and international normalized ratio 0.5. venous blood gas demonstrated pH 7.4, HCO₃ 14.5 mmol/L, PCO₂ 24 mm Hg, and PO₂ 88 mm Hg. Sinus tachycardia with incomplete right bundle-

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branch block was seen on the electrocardiogram. The toxin screen was positive for Serum salicylate level of 45.8 mg/dL, Keppra, cannabinoids, and ethanol. The anion gap was normal throughout the course in the hospital, even with acidosis on basic metabolic panel and venous blood gas (VBG). Salicylate levels in the serum peaked at 81.8 mg/dL after 8 hours. Of note, the Chloride levels mimicked the trends in serum salicylate concentration, peaking at121 mEq/L (Figure).

Immediate treatment was initiated with activated charcoal, 1/2 normal saline with 75 mEq bicarbonate for hydration, alkaliniza- tion, and electrolyte repletion. basic metabolic profile, salicylate levels, and VBGs were done regularly.

Treatment of substance overdose or unknown poisoning in any setting mandates a high level of suspicion. As with our patient, despite the clear history of Keppra overdose, we ran a toxicity screen based on the history and physical findings, keeping in mind the high prevalence of salicylate poisoning. Classically, patients present with a mixed acid-base disorder. Early in the toxidrome, patients are alkalemic (pH N 7.4) due to a primary respiratory alkalosis as a result of medullary stimulation of respiration followed by anion gap metabolic acidosis due to uncoupling of oxidative phosphorylation. The presence of acidemia (pH b 7.4) is concerning because a lower serum pH allows more salicylate to unbind from serum proteins and enter the central nervous system.

In our patient’s case, although the VBG demonstrated acidemia, the anion gap was normal throughout the patient’s hospital stay. In the absence of salicylate levels, the diagnosis would have been missed given the unusual laboratory studies. On review of the possible explanations for this clinical aberration, we found a few case reports describing cases with normal anion gap despite metabolic acidosis due to a laboratory error [2]. It occurs with some ion-specific electrodes in the basic metabolic profile analyzers that mistakenly read salicylate ions as chloride ions leading to an inaccurately high chloride level, mainly attributable to the loss of selectivity toward the end of the operational life of the chloride electrode. The fictitiously elevated chloride levels thus prevented the anion gap from “opening up.” Our hospital uses the Siemens Dimension Vista analyzer, which has been reported to cause such aberrations, as have been others [1-6]. With this analyzer, salicylate levels of 20 and 60 mg/dL are known to produce a 4% and 15% increase, respectively, in the reported chloride levels [1]. Our case shows a linear relationship between salicylate concentrations and chloride values similar to that reported in other articles. Although aggressive fluid resuscitation could have contributed to the hyperchloremia, other Potential causes such as endocrinological and oncological disorders were ruled out on history and examination.

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Day Day Day Day Day Day

1, 1230 1, 0526 1, 0800 1, 1400 1, 2004 2, 0240

Salicylate levels 65.1 79.2 81.8 79 62.7 45.6

Chloride 112 118 121 116 114 110

Anion Gap 6 7 6 4 6 6

Fig. Salicylate and chloride levels-chronological spread.

As an educational point, this case demonstrates the importance of diagnosis of this common poisoning based on strong clinical suspicion, and we recommend caution while depending on anion gap acidosis as a diagnostic tool individually. This is of significance especially in smaller health care setups where toxin screens may not be the norm and salicylate poisoning may be missed as a diagnosis because of this uncommon phenomenon leading to avoidable morbidity and mortality.

Viren Kaul MBBS Syed Haider Imam MBBS Harvir Singh Gambhir MBBS PGY1, Internal Medicine

SUNY Upstate Medical University Syracuse, NY 13202, USA

E-mail addresses: [email protected], [email protected]

Arindam Sangha MS III SUNY Upstate Medical University Syracuse, NY 13202, USA

Sravanthi Nandavaram MBBS

PGY2, Internal Medicine SUNY Upstate Medical University Syracuse, NY 13202, USA

http://dx.doi.org/10.1016/j.ajem.2013.05.031

References

1. Brubacher, Jeffrey R. Salicylism from Topical Salicylates: Review of the Literature Read More: http://informahealthcare.com/doi/abs/10.3109/15563659609013814? journalCode=ctx. Clinical Toxicology. 34.4 (1996):431-436. Print.
2. Jacob J. Falsely normal anion gap in severe salicylate poisoning caused by laboratory interference.Ann Emerg Med 2011;58.3(3):280-1 Web. 11 May. 2013. http://www. sciencedirect.com/science/article/pii/S0196064411001387.
3. Routh JL, Paul WD. Assessment of interference by aspirin with some assays commonly done in the clinical laboratory. Clin Chem 1976;22:837-42.
4. Wang T, Diamandis EP, Lane A, et al. Variable selectivity of the Hitachi chemistry analyzer chloride ion-selective electrode toward interfering ions. Clin Biochem 1994;27:37-41.
5. Mori L, Waldhuber S. Salicylate interference with the Roche Cobas Integra chloride electrode. Clin Chem 1997;43:1249-50.
6. Siemens Dimension Vista(R) System V-Lyte(R) Integrated Multisensor. Reference ManualSiemens Healthcare Diagnostics IncNewark, DE2009.