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False elevation of blood lactate reveals ethylene glycol poisoning
American Journal of Emergency Medicine (2009) 27, 132.e1–132.e2
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Case Report False elevation of blood lactate reveals ethylene glycol poisoning Abstract Ethylene glycol poisoning is a medical emergency. Making a definitive diagnosis is challenging because few institutions have timely access to direct measurement of ethylene glycol. After ingestion, primary metabolism of ethylene glycol takes place in the liver, leading to glycolic acid and glyoxylic acid. These compounds may cross-react with L-lactate oxidase used in blood gas analyzers lactate electrodes to induce false elevation of blood lactate. We present the case of a 47-year-old male patient initially admitted to the intensive care unit for severe lactate acidosis of unknown cause (pH 6.96, lactate, 30 mmol/L). Knowledge of potent artifactual lactate results was the key to the diagnosis of ethylene glycol poisoning, and false lactate measurements were found at the central laboratory on our 3 different blood gas analyzers. In November 2007, a 47-year-old male patient without history of substance abuse or drug therapy consulted to the emergency department for slight confusion. Examination revealed hypothermia (35.4°C), heart rate of 81 beats/min, blood pressure of 163/96 mm Hg, and respiratory rate of 24 breaths/min. The patient obviously had no sign of shock or hepatic failure and was conscious but disorientated. The remaining examination results were not significant. Initial laboratory data revealed the following: pH 7.22; PaO2, 128 mm Hg (room air); PaCO2, 9 mm Hg; HCO3− , 4 mmol/L; lactate, 28.6 mmol/L; Na+, 141 mmol/L; K+, 5.6 mmol/L; Cl−, 103 mmol/L; anion gap, 22 mEq/L; urea, 5.2 mmol/L; creatininemia, 160 μmol/L; and glycemia, 7.1 mmol/L. Toxicology screening was negative for alcohol, salicylates, and acetaminophen. Computed tomography of the brain, chest, and abdomen was unremarkable. The patient was then transferred to the intensive care unit (ICU) for severe lactic acidosis. Thirty minutes after his admission to the ICU, polypnea, confusion, and acidosis increased (pH 6.96; lactate, 30 mmol/L), requiring orotracheal intubation and mechanical ventilation. A gastric lavage did not yield any tablets. Hemodialysis was started. The notion of a potential interference in lactate measurement led to suspected ethylene 0735-6757/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
glycol poisoning [1]: an urgent test revealed an ethylene glycol concentration of 4.8 mmol/L in serum from a blood sample gathered before hemodialysis. The patient was therefore given 1200 mg of intravenous 4-methylpyrazole. He could be extubated 36 hours after ICU admission with a complete neurological recovery but remained oligoanuric and required 3 hemodialysis sessions before his renal failure completely recovered. Ethylene glycol poisoning is a medical emergency. The clinical course is initially characterized by mild symptoms that may gradually develop to produce serious toxicity or even death. Ethylene glycol is rapidly absorbed from the gastrointestinal tract, and primary metabolism takes place in the liver, with 80% metabolized hepatically and 20% excreted unchanged. Ethylene glycol metabolites are responsible for its toxicity, which lead to major metabolic acidosis. Ethylene glycol metabolism is a 4-step process involving alcohol dehydrogenase and aldehyde dehydrogenase, leading to the successive production of glycolic acid, glyoxylic acid, and oxalic acid, which precipitates as calcium oxalate and is deposited in a crystalline form in the kidneys. Initially, in the case of our patient, increased anion gap was apparently explained with increased blood lactate. However, there was no pertinent explanation for such lactic acidosis; this is why an analytic interference was suspected. Indeed, ethylene glycol is not involved in lactate production, and the false elevation of blood lactate is related to ethylene glycol metabolites, mainly glycolic acid but also glyoxylic acid, which have similar chemical structures with L-lactate (Fig. 1). The cause of artifactual blood lactate elevations is method specific. It stems from the incomplete specificity of
Fig. 1
Similar chemical structures of lactate and glycolate.
132.e2 the analytical reagent L-lactate oxidase used in lactate electrodes, which equip many blood gas analyzers, allowing cross-reaction with glycolic acid and glyoxylic acid [1]. The degree of interference varies with L-oxidase–derived species, platforms, and electrode age. Other technologies of lactate measurement [2] may not be affected by ethylene glycol metabolites and can reveal the artifactual error obtained with lactate electrodes. Thus, finding a “lactate gap” using 2 different technologies of lactate measurements, with only one sensitive to glycolic acid/glyoxylic acid, can help to differentiate ethylene poisoning from lactic acidosis. This was not possible in our laboratory, where our 3 blood gas analyzers belong to the Radiometer ABL series (625, 725, and 835; Copenhagen, Denmark) and are equipped with lactate electrodes known to give artifactual results [3]. Fortunately, the notion of a potential interference led the ICU staff to suspect ethylene glycol poisoning and to avoid the misdiagnosis of lactate acidosis. The interference was confirmed later by overloading whole blood with glycolic acid (Sigma-Aldrich, Saint-Quentin-Fallavier, France) at a concentration of 10 mmol/L: lactate concentration increased from 20.9 mmol/L (ABL 625) to 22.7 mmol/L (ABL 725), showing homogenous results. This interference was also found at a lowest level (blood lactate increased by 12.8 mmol/L) using a GEM Premier 4000 (Instrumentation Laboratory, Lexington, MA), a point-of-care analyzer commonly used in emergency units or ICUs. Interestingly, in the setting of potential ethylene glycol poisoning, the use of the lactate electrode may be a simple method used to “monitor” ethylene glycol metabolite levels [4]. In the case of our patient, 24 hours after admission into the ICU, “lactate” dropped to a normal concentration (1.6 mmol/L). Our observation shows that cross-reaction of ethylene glycol metabolites with blood gas analyzers lactate electrodes may delay the diagnosis of poisoning. The
Case Report knowledge of this potential interference was the key to the diagnosis because there was no evident clue of ethylene glycol poisoning in this patient and false lactate measurements were confirmed by our 3 analyzers. Biologists and physicians must be aware of this analytical interference to provide accurate and prompt therapeutics to this masqueraded intoxication. Pascal Pernet PhD Bénédicte Bénéteau-Burnat PhD Michel Vaubourdolle PhD Service de Biochimie A, Hôpital St-Antoine AP-HP, 75571 Paris Cedex 12, France E-mail address: [email protected] Eric Maury MD Georges Offenstadt MD Service de Réanimation Médicale, Hôpital St-Antoine AP-HP, 75571 Paris Cedex 12, France
doi:10.1016/j.ajem.2008.04.029
References [1] Shirey T, Sivilotti M. Reaction of lactate electrodes to glycolate. Crit Care Med 1999;27:2305-7. [2] Graïne H, Toumi K, Roullier V, et al. Interference of ethylene glycol on lactate assays. Ann Biol Clin 2007;4:421-4. [3] Brindley PG, Butler MS, Cembrowski G, et al. Falsely elevated pointof-care lactate measurement after ingestion of ethylene glycol. CMAJ 2007;176:1097-9. [4] Porter WH, Crellin M, Rutter PW, et al. Interference by glycolic acid in the Beckman synchron method for lactate: a useful clue for unsuspected ethylene glycol intoxication. Clin Chem 2000;46:874-5.
www.elsevier.com/locate/ajem
Case Report False elevation of blood lactate reveals ethylene glycol poisoning Abstract Ethylene glycol poisoning is a medical emergency. Making a definitive diagnosis is challenging because few institutions have timely access to direct measurement of ethylene glycol. After ingestion, primary metabolism of ethylene glycol takes place in the liver, leading to glycolic acid and glyoxylic acid. These compounds may cross-react with L-lactate oxidase used in blood gas analyzers lactate electrodes to induce false elevation of blood lactate. We present the case of a 47-year-old male patient initially admitted to the intensive care unit for severe lactate acidosis of unknown cause (pH 6.96, lactate, 30 mmol/L). Knowledge of potent artifactual lactate results was the key to the diagnosis of ethylene glycol poisoning, and false lactate measurements were found at the central laboratory on our 3 different blood gas analyzers. In November 2007, a 47-year-old male patient without history of substance abuse or drug therapy consulted to the emergency department for slight confusion. Examination revealed hypothermia (35.4°C), heart rate of 81 beats/min, blood pressure of 163/96 mm Hg, and respiratory rate of 24 breaths/min. The patient obviously had no sign of shock or hepatic failure and was conscious but disorientated. The remaining examination results were not significant. Initial laboratory data revealed the following: pH 7.22; PaO2, 128 mm Hg (room air); PaCO2, 9 mm Hg; HCO3− , 4 mmol/L; lactate, 28.6 mmol/L; Na+, 141 mmol/L; K+, 5.6 mmol/L; Cl−, 103 mmol/L; anion gap, 22 mEq/L; urea, 5.2 mmol/L; creatininemia, 160 μmol/L; and glycemia, 7.1 mmol/L. Toxicology screening was negative for alcohol, salicylates, and acetaminophen. Computed tomography of the brain, chest, and abdomen was unremarkable. The patient was then transferred to the intensive care unit (ICU) for severe lactic acidosis. Thirty minutes after his admission to the ICU, polypnea, confusion, and acidosis increased (pH 6.96; lactate, 30 mmol/L), requiring orotracheal intubation and mechanical ventilation. A gastric lavage did not yield any tablets. Hemodialysis was started. The notion of a potential interference in lactate measurement led to suspected ethylene 0735-6757/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
glycol poisoning [1]: an urgent test revealed an ethylene glycol concentration of 4.8 mmol/L in serum from a blood sample gathered before hemodialysis. The patient was therefore given 1200 mg of intravenous 4-methylpyrazole. He could be extubated 36 hours after ICU admission with a complete neurological recovery but remained oligoanuric and required 3 hemodialysis sessions before his renal failure completely recovered. Ethylene glycol poisoning is a medical emergency. The clinical course is initially characterized by mild symptoms that may gradually develop to produce serious toxicity or even death. Ethylene glycol is rapidly absorbed from the gastrointestinal tract, and primary metabolism takes place in the liver, with 80% metabolized hepatically and 20% excreted unchanged. Ethylene glycol metabolites are responsible for its toxicity, which lead to major metabolic acidosis. Ethylene glycol metabolism is a 4-step process involving alcohol dehydrogenase and aldehyde dehydrogenase, leading to the successive production of glycolic acid, glyoxylic acid, and oxalic acid, which precipitates as calcium oxalate and is deposited in a crystalline form in the kidneys. Initially, in the case of our patient, increased anion gap was apparently explained with increased blood lactate. However, there was no pertinent explanation for such lactic acidosis; this is why an analytic interference was suspected. Indeed, ethylene glycol is not involved in lactate production, and the false elevation of blood lactate is related to ethylene glycol metabolites, mainly glycolic acid but also glyoxylic acid, which have similar chemical structures with L-lactate (Fig. 1). The cause of artifactual blood lactate elevations is method specific. It stems from the incomplete specificity of
Fig. 1
Similar chemical structures of lactate and glycolate.
132.e2 the analytical reagent L-lactate oxidase used in lactate electrodes, which equip many blood gas analyzers, allowing cross-reaction with glycolic acid and glyoxylic acid [1]. The degree of interference varies with L-oxidase–derived species, platforms, and electrode age. Other technologies of lactate measurement [2] may not be affected by ethylene glycol metabolites and can reveal the artifactual error obtained with lactate electrodes. Thus, finding a “lactate gap” using 2 different technologies of lactate measurements, with only one sensitive to glycolic acid/glyoxylic acid, can help to differentiate ethylene poisoning from lactic acidosis. This was not possible in our laboratory, where our 3 blood gas analyzers belong to the Radiometer ABL series (625, 725, and 835; Copenhagen, Denmark) and are equipped with lactate electrodes known to give artifactual results [3]. Fortunately, the notion of a potential interference led the ICU staff to suspect ethylene glycol poisoning and to avoid the misdiagnosis of lactate acidosis. The interference was confirmed later by overloading whole blood with glycolic acid (Sigma-Aldrich, Saint-Quentin-Fallavier, France) at a concentration of 10 mmol/L: lactate concentration increased from 20.9 mmol/L (ABL 625) to 22.7 mmol/L (ABL 725), showing homogenous results. This interference was also found at a lowest level (blood lactate increased by 12.8 mmol/L) using a GEM Premier 4000 (Instrumentation Laboratory, Lexington, MA), a point-of-care analyzer commonly used in emergency units or ICUs. Interestingly, in the setting of potential ethylene glycol poisoning, the use of the lactate electrode may be a simple method used to “monitor” ethylene glycol metabolite levels [4]. In the case of our patient, 24 hours after admission into the ICU, “lactate” dropped to a normal concentration (1.6 mmol/L). Our observation shows that cross-reaction of ethylene glycol metabolites with blood gas analyzers lactate electrodes may delay the diagnosis of poisoning. The
Case Report knowledge of this potential interference was the key to the diagnosis because there was no evident clue of ethylene glycol poisoning in this patient and false lactate measurements were confirmed by our 3 analyzers. Biologists and physicians must be aware of this analytical interference to provide accurate and prompt therapeutics to this masqueraded intoxication. Pascal Pernet PhD Bénédicte Bénéteau-Burnat PhD Michel Vaubourdolle PhD Service de Biochimie A, Hôpital St-Antoine AP-HP, 75571 Paris Cedex 12, France E-mail address: [email protected] Eric Maury MD Georges Offenstadt MD Service de Réanimation Médicale, Hôpital St-Antoine AP-HP, 75571 Paris Cedex 12, France
doi:10.1016/j.ajem.2008.04.029
References [1] Shirey T, Sivilotti M. Reaction of lactate electrodes to glycolate. Crit Care Med 1999;27:2305-7. [2] Graïne H, Toumi K, Roullier V, et al. Interference of ethylene glycol on lactate assays. Ann Biol Clin 2007;4:421-4. [3] Brindley PG, Butler MS, Cembrowski G, et al. Falsely elevated pointof-care lactate measurement after ingestion of ethylene glycol. CMAJ 2007;176:1097-9. [4] Porter WH, Crellin M, Rutter PW, et al. Interference by glycolic acid in the Beckman synchron method for lactate: a useful clue for unsuspected ethylene glycol intoxication. Clin Chem 2000;46:874-5.