Osmolal Gap without Anion Gap in a 43-Year-Old Man

Abstract

A 43-year-old man presented to the emergency department (ED) 3 2 h after ingesting 10 oz of antifreeze mixed with Gatorade in a suicide attempt. The antifreeze was green, of an unknown brand, and purchased at a local gas station. He subsequently confessed to his wife, who brought him to a community hospital ED. He denied abdominal pain, nausea, vomiting, urinary symptoms, or visual changes. Initial laboratory tests (Table 1) With the advice of the local Poison Control Center, the patient was given 15 mg/kg fomepizole intravenously. He was placed on suicide precautions and transferred to a tertiary care center for further evaluation and treatment. On arrival at the tertiary care ED 8 h after ingestion and 3 h after fomepizole administration, the patient had a normal mental status and normal vital signs. Thiamine (100 mg), folic acid (50 mg), and pyridoxine (50 mg) were administered intravenously as cofactors for secondary metabolic pathways. At that time, laboratory test results (Table 1) were clinically relevant for the following: arterial whole-blood pH, 7.39; PCO 2 , 28 mmHg (3.7 kPa); serum bicarbonate, 18 mmol/L; creatinine, 1.1 mg/dL (97.2 mol/L); lactate, 5.3 mmol/L; anion gap, 14 mmol/L; and osmolal gap, 72 mOsm/kg. No crystals were visible in the urine. CASE FOLLOW-UPGiven the improving anion gap and the lack of clinically relevant acidemia, there was debate about whether this patient had actually ingested ethylene glycol (EG) or had instead ingested propylene glycol (found in "safer" antifreezes) or isopropyl alcohol. Therefore, a test for the serum concentration of EG was ordered for confirmation. The sample for measurement of EG by gas chromatography had to be sent by courier to the closest clinical laboratory offering the test, with the results expected in 4 -8 h. While the sample was en route for testing by gas chromatography, the hospital pathologist performed a modified version of a commercially available veterinary enzymatic assay. This test had been validated by our laboratory, and the results of these studies have been published (1 ). The serum concentration of EG (Table 1) measured by enzymatic assay was 308 mg/dL (49.6 mmol/L). On the basis of this information, the patient was continued on fomepizole, and plans were made for hemodialysis. Ten hours after admission, the gas chromatography result indicated an EG concentration of 315 mg/dL (50.9 mmol/L), in close agreement with the results of the enzymatic assay (the gas chromatography results were negative for methanol and isopropyl alcohol). After hemodialysis was performed, the patient's postdialysis serum showed an osmolal gap of 6 mOsm/kg and an EG concentration of 50 mg/dL (8.2 mmol/L). After a second hemodialysis course, the EG concentration according to the enzymatic assay was 1.4 mg/dL (0.2 mmol/L); the fomepizole treatment was then discontinued. The patient's renal function remained normal, and he recovered completely. He was discharged from the hospital to a psychiatric treatment facility.

Diagnosis of toxic alcohols: limitations of present methods

“…therefore, although the osmol gap is often helpful in monitoring the patient, the clinician should be aware of its possible limitations. 37 furthermore, an increase in the osmol gap, even when significant, might not always indicate the presence of toxic alcohols. Other disorders can be associated with an increase in the osmol gap.…”

“…37 Based on the above discussion, the osmol gap might not always accurately reflect alcohol concentration. therefore, although the osmol gap is often helpful in monitoring the patient, the clinician should be aware of its possible limitations.…”

“…35 Based on these findings, in part, many clinicians have considered any value for the osmol gap less than 10 mOsm/kg/H 2 O as consistent with the absence of foreign osmotically active particles, whereas values greater than 10 mOsm/kg/H 2 O are consistent with accumulation of foreign osmotically active substances in the blood. 31,[36][37][38] Complicating the issue, the normal serum osmol gap reported by various clinical laboratories can be substantially different than 8 or 9 mOsm/kg/H 2 O. for example, the mean serum osmol gap in 10 adult patients without any apparent disease was  1.5  2.5 mOsm/kg/H 2 O. 39 felton et al 37 found that the highest reported value for the osmol gap in 40 normal adults was 2 mOsm/kg/H 2 O; the mean and range of values were not reported.…”

“…31,[36][37][38] Complicating the issue, the normal serum osmol gap reported by various clinical laboratories can be substantially different than 8 or 9 mOsm/kg/H 2 O. for example, the mean serum osmol gap in 10 adult patients without any apparent disease was  1.5  2.5 mOsm/kg/H 2 O. 39 felton et al 37 found that the highest reported value for the osmol gap in 40 normal adults was 2 mOsm/kg/H 2 O; the mean and range of values were not reported. Also, examination of the osmol gap in 192 normal children from a single hospital revealed it to vary from  13.5 to  8.9 mOsm/kg/H 2 O.…”

“…26,30 Some experts have suggested initiation of treatment such as fomepizole based on high suspicion of the diagnosis and/or the presence of metabolic acidosis of unknown cause. 37,47 After an initial dose of fomepizole, its concentration will remain above the inhibitory threshold of the enzyme ADH for 24 h or longer. 48,49 this approach will allow sufficient time for definitive detection of a toxic alcohol.…”