Case Report

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American Journal of Emergency Medicine

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Reversal of refractory severe lactic acidosis by thiamine replacement

Abstract

We describe 2 cases of severe refractory lactic acidosis after optimi- zation of the volume status and vasoactive drugs that were promptly re- versed by intravenous thiamine administration. The emergency physician must be aware of the diagnosis of Thiamine deficiency (beri- beri) in critically ill patients with refractory hyperlactatemia without apparent cause.

A 44-year-old man, alcoholic, without other diseases, was admitted to the emergency department (ED) with acute respiratory failure and underwent endotracheal intubation and mechanical ventilation. Physi- cal examination showed hypotension (60 x 30 mm Hg) and tachycardia (120 beats per minute). Laboratory tests showed severe metabolic aci- dosis (pH: 6.85, pCO₂: 14 mm Hg, bicarbonate: 03 mmol/L, basic excess:

-26) and hyperlactatemia (21 mmol/L). Because of the severity of the case, empiric antibiotic therapy was started despite not identifying any infectious cause. He did not respond to fluid resuscitation (2000 mL of 0.9% saline), requiring increasing doses of norepinephrine and vasopressin. After 2 hours, there was no improvement in lactate levels, and dobutamine was started. Bedside echocardiography showed cardiac chambers with normal dimensions, left ventricle with hyperdynamic pattern, and left ventricular ejection fraction of 85%. Be- cause of the maintenance of important acidosis with hyperdynamic cir- culation pattern and alcohol abuse history, it was decided to carry out intravenous thiamine. After intravenous thiamine (400 mg), a dramatic reduction in lactate levels was observed in 6 hours (Lactate clearance: 70%) with Rapid reduction and suspension of vasoactive drugs. The pa- tient was removed from mechanical ventilation in the next day and was discharged from hospital after 5 days (Figure).

A 71-year-old man, alcoholic, without other diseases, was admitted to the ED because of dyspnea associated with abdominal pain and vomiting. Physical examination showed mental confusion (Glasgow Coma Scale: 14), tachycardia (121 beats per minute), tachypnea, and ar- terial blood pressure of 90 x 60 mm Hg. Laboratory tests showed severe metabolic acidosis (pH: 7.00, pCO₂: 15 mm Hg, bicarbonate: 04 mmol/L, basic excess: -24) with hyperlactatemia (18 mmol/L). Empiric antibi- otic therapy and Fluid replacement were started despite not identifying any infectious cause. He presented cardiorespiratory arrest in pulseless electrical activity quickly reversed after 200 mL of 8.4% sodium bicar- bonate. After the cardiac arrest, he presented hemodynamic instability and needed vasoactive drugs. The result of the bedside echocardiogra- phy was normal. The emergency physician decided to use intravenous thiamine administration (400 mg). After 6 hours, a dramatic reduction in lactate levels (lactate clearance: 88%) was observed associated with pH normalization. The patient was removed from mechanical

ventilation in the next day and was discharged from hospital after 7 days without any Neurological sequelae.

tissue hypoxia associated with states of circulatory shock seems to be the primary mechanism responsible for hyperlactatemia, but other less common causes can lead to high lactate levels. We report 2 cases of severe lactic acidosis probably secondary to thiamine deficiency with dramatic response to vitamin replacement.

In mitochondria, thiamine participates as a coenzyme of pyruvate dehydrogenase, which leads to oxidative pyruvate decarboxylation to acetyl-CoA and as a coenzyme of alpha-ketoglutarate dehydrogenase responsible for the decarboxylation of alpha-ketoglutarate to succinyl- CoA (key enzymes of the Krebs cycle). Thiamine also acts as a coenzyme of transketolase via the pentose monophosphates, which participates in the nucleic acid synthesis. Thiamine deficiency causes a blockage in the conversion of pyruvate to acetyl-CoA, and therefore, the production of adenosine triphosphate is restricted to the anaerobic phase (glycolysis); this way, the pyruvate is converted to lactate leading to significant hyperlactatemia, as observed in these cases [1,2].

Thiamine deficiency is rare in the West, with few cases reported in the literature, almost exclusively related to alcohol consumption. How- ever, recent evidence suggests that thiamine deficiency may be underestimated especially for nonalcoholic patients. An observational study showed that 33% of the patients admitted with heart failure had thiamine deficiency [3]. Another recent investigation with 156 septic patients admitted to an intensive care unit showed that 20% had a thia- mine deficiency, and in this group, a mortality rate of 72% was observed compared with a mortality rate of 50% in the group without this vitamin Deficiency [4].

Laboratory diagnosis is difficult because the thiamine dosage or erythrocyte transketolase activity was not widely available; these tests have low specificity, and they are rarely used in the context of the ED [5]. The emergency physician should suspect thiamine deficiency in crit- ically ill patients with severe lactic acidosis without an apparent cause or persistent acidosis despite appropriate interventions, mainly in alco- holic patients and in hypermetabolic conditions (sepsis, trauma, etc) and when unexplained heart failure or neurological signs are addition- ally observed in this setting. In this situation, empirical intravenous thi- amine replacement is indicated. The dramatic clinical improvement is often in these cases, as noted in these 2 cases [6,7]. Despite not having carried out any confirmatory laboratory test of thiamine deficiency in these 2 cases, the significant clinical and laboratory improvement, mainly of the lactic acidosis, with thiamine replacement reinforces this diagnosis.

In conclusion, thiamine deficiency can cause severe clinical condi- tions, including circulatory shock and hyperlactatemia. The emergency

0735-6757/(C) 2016

Figure. Graph showing the evolution of lactate and bicarbonate levels after intravenous administration of thiamine in a patient with refractory severe lactic acidosis.

physician must be aware of the diagnosis of thiamine deficiency (beri- beri) in critically ill patients with refractory hyperlactatemia without apparent cause.

Sources of funding

None declared.

Conflict of interest

None.

Maira Benatti, MD Antonio Pazin-Filho, MD, PhD Carlos Henrique Miranda, MD, PhD*

Division of Emergency Medicine of the Department of Internal Medicine of the Ribeirao Preto School of Medicine of the Sao Paulo University

*Corresponding author at: Centro Integrado de Emergencias em Saude, Unidade de Emergencia-HCFMRP-USP, Rua Bernardino de Campos, 1000, Ribeirao Preto, SP 14020-670, Brazil

Tel.: +1 55 16 36021240; fax: +1 55 16 36021240

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2016.09.062

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