Osmolal gap

Garcia-Morales EJ, Cariappa R, Parvin CA. Osmole gap in neurosurgical-neurosurgical intensive care unit its normal value, calculation, and relationship with mannitol serum concentrations. Crit Care Med 2004 32(4) 986-991. 

Intoxication may present as inebriation and drowsiness similar to ethanol use. Other symptoms are vomiting, diarrhea, delirium and agitation, back and abdominal pain, and clammy skin. Toxic effects usually follow a latent period of several hours. Formate inhibits mitochondrial cytochromes resulting in neurotoxicity. Ocular signs include blurred vision, dilated pupils, and direct retinal toxicity with optic disc hyperemia and ultimately permanent blindness [91]. Cerebral hemorrhagic necrosis has been reported [92]. Severe poisoning may result in Kussmaul respiration, inspiratory apnea, coma, and death. Urine samples may have the characteristic smell of formaldehyde. An elevated serum osmolal gap from methanol will be evident early in presentation but may disappear after approximately 12 hours. At this time, an elevated anion gap metabolic acidosis from retained formate may be evident. 

Hemodialysis corrects any metabolic acidosis while removing methanol and formate [97] and should be considered with evidence of organ toxicity, presence of acidosis, and methanol levels greater than 50 mg/ dL. Fomepizole is dialyzable (see next section). Closure of the osmolal gap correlates with methanol removal and can be followed if methanol levels are unavailable or... 

Early laboratory findings include a high serum osmolal gap from the ethylene glycol. An extreme metabolic acidosis with greatly elevated anion gap follows, principally from glycolic acid [100]. Hypocalcemia and hyperkalemia may be evident and urinalysis may reveal calcium oxalate crystalluria, hematuria, and proteinuria. 

Hunderi OH, Hovda KE, Jacobsen D. Use of the osmolal gap to guide the start and duration of dialysis in methanol poisoning. ScandJ Urol Nephrol. 2006 40 70-74... 

Steinhart B. Case report severe ethylene glycol intoxication with normal osmolal gap—"a chilling thought". J Emerg Med 1990 8 583. 

Ammar KA, Heckerling PS. Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion importance of the osmolal gap. Am J Kidney Dis 1996 27 130. 

Geller RJ, Spyker DA, Herold DA, Bruns DE. Serum osmolal gap and ethanol concentration a simple and accurate formula. J Toxicol Clin Toxicol 1986 24 77-84. 

The 9mOsmol/kg added to the above equation represents the contribution of other osmoticaUy active substances in plasma, such as K", Ca " ", and proteins, and 1.86 is two times the osmotic coefficient of Na, reflecting the contributions of both Na and CT. The reference interval for plasma osmolality is 275 to 300mOsmol/kg. Comparison of measured osmolality with calculated osmolality can help identify the presence of an osmolal gap, which can be important in determining the presence of exogenous osmotic substances. Comparison of calculated and measured osmolalities can also confirm or rule out suspected pseudohyponatremia caused by the previously discussed electrolyte exclusion effect. 

An important clinical difference between the vapor pressure technique and the freezing point depression osmometer is the failure of the former to include in its measurement of total osmolality any volatile solutes present in the serum. Substances such as ethanol, methanol, and iso-propanol are volatile, and thus escape from the solution and increase the vapor pressure instead of lowering the vapor pressure of the solvent (water). This makes use of vapor pressure osmometers impractical for identifying osmolal gaps in acid-base disturbances (see Chapter 46). Thus use of this type of osmometer cannot be recommended for most clinical laboratories. 

Glasser DS. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. Ann Emerg Med 1996 27 343-6. 

Ingested ethylene glycol is metabolized to glycolic and oxalic acids and other acidic metabolites. Its metabolism leads to an acidosis with high anion and osmolal gaps. Accumulation of toxic metabohtes may contribute to lactic acid production that further contributes to the acidosis. Precipitation of calcium oxalate and hippurate crystals in the urinary tract... 

The osmolality of stool "water wiU normally be that of serum (i.e., 290mosm/kg), but the contribution of electrolytes and of nonelectrolytes to the total osmolality will vary depending on the cause of the diarrhea. Fecal osmotic (osmolal) gap (FOG) expresses the difference between the theoretical normal osmolality (290 mosm/kg) and the contribution of Na and as follows ... 

Butoxyethanol has been shown to increase human plasma osmolality in vitro (Browning and Curry 1992). The osmolal gap is frequently used in the evaluation of a patient who has accidentally or intentionally ingested a glycol ether or related compound (Gijsenbergh et al. 1989). The presence of an elevated osmolal gap indicates the presence of significant blood levels of the toxic compound. This is not an indicator that is specific to 2-butoxyethanol or 2-butoxyethanol acetate and should be used in conjunction with other biomarker assays. 

The relative contribution of ethanol in cases of coma, especially where other drugs and/or head injury arc present, may be difficult to distinguish. Blood ethanol determinations arc the best guide. Where these are not available, plasma osmolality measurement and calculation of the osmolal gap may help. 

An elevated serum osmolality and an increased osmolal gap can be of diagnostic vaiue in acute ethanol poisoning. 

This boy s calculated osmolality is approximately 206 mmol/kg. Thus, the osmolal gap is approximately 76 mmol/lkg. This has arisen because of his severe hyperlipidaemia which has caused pseudohyponatraemia. In severe hyperlipidaemia the plasma water concentration is decreased due to the abnormally high contribution of the lipoproteins to the plasma volume. As a result, the concentration of sodium per litre of serum is decreased as the sodium is not present in the lipoproteins but will have a normal concentration in the serum water. 

This simple formula only holds if the serum concentration of urea and glucose are within the reference ranges. If either or both are abnormally high, the concentration of either or both (in mmol/l) must be iiddcd in to give the calculated osmolality.. Sometimes there is an apparent difference betw een the measured and calculated osmolality. This is known as the osmolal gap (p. 17). 

A large discrepancy between the measured osmolality and the calculated osmolality is called the osmolal gap (seep. 13) and sugge.sts the presence of a significant contributor to the osmolality unaccounted for in the calculation. In practice, this is almost always due to the presence of ethanol in the blood. Very occasionally, however, it may be due to... 

If a low sodium concentration is suspicious, measure the serum osmolality. Know ing the glucose and urea concentration, the calculated osmolality can also be obtained. If the two results differ (that is, if there is a significant osmolal gap), the measured. sodium... 

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