PRACTICE LESSON OF THE WEEK

The importance of the osmolality gap in ethylene glycol intoxication Rimke Oostvogels,1 Hans Kemperman,2 Isabelle Hubeek,2 Edith WMT ter Braak1 1

Department of Internal Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands 2 Department of Clinical Chemistry and Haematology, University Medical Center Utrecht Correspondence to: R Oostvogels [email protected] Cite this as: BMJ 2013;347:f6904 doi: 10.1136/bmj.f6904

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BMJ | 7 DECEMBER 2013 | VOLUME 347

In patients with very high lactate levels, calculate the osmolality gap, as ethylene glycol poisoning may falsely elevate lactate levels In patients with a suspected intoxication of unknown agents it is vital to discover the presence and nature of the ingested poison as soon as possible to assess the risk of life threatening symptoms and to carry out proper thera­ peutic actions. We report a case in which the diagnostic process was hindered by abnormal laboratory findings due to analytical interference of the toxic agent ethylene glycol and its metabolites with lactate measurement. Accurate clinical reasoning with simple calculation of the osmolality gap, however, led to the right diagnosis.

Case report A 32 year old woman was admitted to the emergency department of our hospital because of somnolence, pre­ sumably after an attempted suicide at home. She was accompanied by two social workers from the psychiatric facility where she was treated on an outpatient basis for dis­ sociative and depressive disorders. They brought all medi­ cation boxes they had found in the patient’s house and a list of current prescriptions, which included tranylcypromine, quetiapine, temazepam, clonazepam, cyproheptadine, mel­ atonin, oxazepam, levomepromazine, and pipamperone. During initial assessment, the patient’s Glasgow Coma Scale was 11/15, she was haemodynamically sta­ ble (blood pressure 140/85 mm Hg with a regular heart rate of 90 beats/min) with a body temperature of 37.3°C. Oxygen saturation was normal with a respiration rate of 16 breaths/min. Besides somnolence, physical exami­ nation showed no abnormalities. Initially, we suspected intoxication with one or more of the prescribed drugs, overdoses of which may readily cause somnolence. How­ ever, no evidence for such intoxication (such as empty medication boxes or strips) nor bottles or packages from other toxic substances had been found with the patient. Laboratory results on admission showed a metabolic acidosis with partial respiratory compensation and a plasma lactate concentration of 25.9 mmol/L. Table 1 shows all the test results, plus reference values. However, no clinical clues for conditions that could explain this severe lactic acidosis (such as shock, hypoxia, lactatae­ mia inducing drugs (such as metformin or antiretroviral drugs), or sepsis) were present. We then calculated the anion gap and the osmolality gap using the formulas provided in table 2. Both gaps were elevated, with values of 23 mmol/L and 84 mmol/kg respectively. Although lactic acidosis might explain an elevated anion gap, it could not account for the extremely high osmolality gap. In severe lactic acidosis some

el­evation of the osmolality gap may occur, probably as a result of smaller side products of glycogen breakdown, but this elevation seldom exceeds 10 mmol/kg.1 Possible other causes of an elevated osmolality gap are ethanol intoxication, pseudohyponatraemia due to severe hyper­ proteinaemia or hyperlipidaemia, chronic renal failure, and intoxication with toxic alcohols or glycols. However, in ethanol intoxication or pseudohyponatraemia normally no high anion gap metabolic acidosis is seen.1 As renal function was normal at that time, we concluded that fur­ ther testing for methanol and ethylene glycol was indi­ cated. The level of ethylene glycol was found to be 5.3 g/L, methanol was not detected. This concentration of ethyl­ ene glycol almost exactly matched the osmolality gap of 84 mmol/kg, as calculated with the following formula: Concentration (g/L)=(osmolality gap)× (molecular weight/1000), with the molecular weight of ethylene glycol being 62 g/mol. In the meantime, the patient had been transferred to the intensive care unit, and mechanical ventilation was started because of coma (Glasgow coma scale 5/15). Also, renal function had deteriorated, with an increase of the creatinine level to 193 μmol/L initially and later 280 μmol/L with the development of anuria. Im­mediately Table 1 | Patient’s laboratory blood test values at admission to hospital Laboratory test

Value at admission

Reference range

pH PaCO2 (mm Hg) PaO2 (mm Hg) Bicarbonate (mmol/L) Sodium (mmol/L) Potassium (mmol/L) Calcium (mmol/L) Chloride (mmol/L) Creatinine (μmol/L) Blood urea nitrogen (mmol/L) Glucose (mmol/L) Lactate (mmol/L) Plasma osmolality (mmol/kg) Haemoglobin (mmol/L) White cell count (×109/L) Platelets (×109/L)

7.22 22 133 9.1 142 3.8 2.15 110 100 5.2 6.8 25.9 380 7.4 5.2 240

7.37–7.45 32–43 70–100 20.0–26.0 136–146 3.8–5.0 2.20–2.60 99–108 58–103 3.0–7.5 3.6–5.6 0.0–2.2 280–295 7.4–9.6 4.0–10.0 150–450

Table 2 | Formulas for calculation of anion gap and osmolality gap Formula (all serum concentrations in mmol/L)

Anion gap

Test value

Sodium− 23 mmol/L (chloride+bicarbonate) Osmolality Measured osmolality− 84 mmol/kg gap ((2×sodium)+BUN+glucose)

Reference values

5–11 mmol/L