Elevated Osmolal Gap in a Case of Multiple Myeloma.

BACKGROUND: The estimated serum osmolality is a measurement of solutes in the blood, including sodium, glucose, and urea, but also includes ethanol and toxic alcohols (e.g., methanol, ethylene glycol, diethylene glycol, isopropyl alcohol, propylene glycol) when present. These rarely measured toxic alcohols can elevate the serum osmolality, giving the true measured osmolality. The difference between that and a calculated osmolality is the osmolal gap, which can be elevated in many clinical scenarios such as renal failure, ingestion of toxic alcohols, diabetic ketoacidosis, shock, and others. CASE REPORT: We report a patient with a history of alcohol use disorder who came to the Emergency Department with an abnormally elevated osmolal gap in the setting of altered mental status. The patient's increased osmolal gap was further investigated while he was promptly treated with fomepizole, thiamine, and urgent hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss the differential diagnosis for substances that increase the osmolal gap with respective ranges of elevation. This case demonstrates that although osmolal gap elevation is often attributed to the presence of toxic alcohols, other common etiologies may account for the gap, including acute renal failure and multiple myeloma.

Acute Ethanol Intoxication: Αn Overlooked Cause of High Anion Gap Metabolic Acidosis With a Marked Increase in Serum Osmolal Gap.

Measurement of serum osmolal gap is a useful tool in suspected toxic alcohol ingestion. Normal levels of osmolal gap are typically <10 mOsm/kg). Osmolal gap >20 mOsm/kg is usually caused by ingestion of methanol, ethylene glycol, isopropanol, propylene glycol, diethylene glycol, or organic solvents such as acetone but rarely of ethanol alone. Herein, we describe the case of a severe ethanol intoxication presenting with a marked increase in the osmolal gap. An 18-year-old male was referred to the emergency department of our hospital, in a comatose state, following binge drinking. blood gas analysis revealed a high anion gap metabolic acidosis. In addition, it was found an extremely elevated osmolal gap of 91 mOsm/kg. The increment of the osmolal gap and the high anion gap acidosis could not be attributed to methanol/ethylene glycol intoxication, alcoholic ketoacidosis, or other cause of acidosis. The calculated osmolal concentration of ethanol was 91 mOsm/kg (osmolal concentration of ethanol is equal to the serum ethanol levels (mg/dL) divided by 3.7). Thus, the increase in the osmolal gap was a result of ethanol intoxication solely. Acute, isolated, ethanol intoxication may be a rare cause of a marked increase of osmolal gap with high anion gap metabolic acidosis. Clinicians should be alerted to the possibility of acute ethanol intoxication in a patient presenting with high anion gap metabolic acidosis and an extremely elevated osmolal gap. Toxicologic screen tests should be performed to identify the aetiology of the gap rise and proper therapy should be administered.

Moderate hyperosmolar hyponatremia caused by excessive off-label use of icodextrin during peritoneal dialysis.

Icodextrin use during the long dwell of a peritoneal dialysis (PD) regimen is commonly used to increase ultrafiltration. Its use may cause a mild and clinically insignificant degree of hyponatremia. We describe a patient who was admitted twice to our medical center on an atypical continuous ambulatory peritoneal dialysis (CAPD) regimen utilizing solely icodextrin with 2 exchanges (12-hour dwells). On both admissions, he had hyperosmolar hyponatremia in the 120-mmol/L range with a large osmolal gap. After icodextrin was stopped and his PD prescription was switched to dextrose solutions, both hyponatremia corrected and the osmolal gap quickly disappeared. The accumulation of osmotically active solute in extracellular fluids results in efflux of water from the cellular compartment and produces both hyponatremia and hypertonicity [1]. This tonic effect occurs most frequently with hyperglycemia, but other substances can also cause this, including mannitol, sorbitol, glycine, and maltose [1, 2]. In this report, we present a patient with end-stage renal disease (ERSD) on an atypical off-label PD regimen utilizing solely icodextrin solutions who developed hyperosmolar hyponatremia in the 120-mmol/L range, with a large osmolal gap. This appeared to be due to absorbed metabolites of icodextrin, mainly maltose.

Serum osmolality and hyperosmolar states.

Serum osmolality is the sum of the osmolalities of every single dissolved particle in the blood such as sodium and associated anions, potassium, glucose, and urea. Under normal conditions, serum sodium concentration is the major determinant of serum osmolality. Effective blood osmolality, so-called blood tonicity, is created by the endogenous (e.g., sodium and glucose) and exogenous (e.g., mannitol) solutes that are capable of creating an osmotic gradient across the membranes. In case of change in effective blood osmolality, water shifts from the compartment with low osmolality into the compartment with high osmolarity in order to restore serum osmolality. The difference between measured osmolality and calculated osmolarity forms the osmolal gap. An increase in serum osmolal gap can stem from the presence of solutes that are not included in the osmolarity calculation, such as hypertonic treatments or toxic alcoholic ingestions. In clinical practice, determination of serum osmolality and osmolal gap is important in the diagnosis of disorders related to sodium, glucose and water balance, kidney diseases, and small molecule poisonings. As blood hypertonicity exerts its main effects on the brain cells, neurologic symptoms varying from mild neurologic signs and symptoms to life-threatening outcomes such as convulsions or even death may occur. Therefore, hypertonic states should be promptly diagnosed and cautiously managed. In this review, the causes and treatment strategies of hyperosmolar conditions including hypernatremia, diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, hypertonic treatments, or intoxications are discussed in detail to increase awareness of this important topic with significant clinical consequences.

Derivation and validation of a new formula for plasma osmolality estimation.

BACKGROUND: Plasma osmolality is a physic and chemical property of interest in emergency medicine. This magnitude can be measured at the laboratory, but it is usually estimated with equations. A huge variety of formulas for calculating osmolality have been published, most of them relying on sodium, urea and glucose. The purpose of this study is to develop a new equation for plasma osmolality calculation. In addition we assess the new equation in a sample of healthy individuals. METHODS: We used results of sodium, potassium, glucose, urea and osmolality recovered from our patient's database. Multivariate lineal regression was carried-out, considering sodium and potassium as separated variables and as unique variable. In a second phase the obtained equations were tested in a sample of healthy blood-donors. Osmolality was measured by freezing point depression. RESULTS: In the first phase, 1362 plasma determinations for sodium, potassium, glucose, urea and osmolality were analyzed. All of included variables had a significant correlation with measured osmolality, being the highest correlation with sodium plus potassium and the lowest one was with potassium alone. The formulas obtained for the osmolality estimation were 1.86*Na + 1.6*(Glucose/18) + 1.12*(Urea/6) + 21 (A) and 1.88*(Na + K) + 1.59*(Glucose/18) + 1.08*(Urea/6) + 10.6 (B). Assess of the new equations in a sample of healthy individuals showed better results than equations previously published. The lowest difference versus measured osmolality was produced by formula B. CONCLUSION: The equations produced in this study perform better in the estimation of plasma osmolality than previously published formulas. We recommend introducing formula B in the clinical chemistry routine.

Comparative Impact of Isolated Ultrafiltration and Hemodialysis on Fluid Distribution: A Bioimpedance Study.

INTRODUCTION: Isolated ultrafiltration (IUF) is an alternative treatment for diuretic-resistant patients with fluid retention. Although hemodialysis (HD) predominantly decreases extracellular water (ECW), the impact of IUF on fluid distribution compared with HD remains unclear. METHODS: We compared the effect of HD (n = 22) and IUF (n = 10) sessions on the body fluid status using a bioimpedance analysis device (InBody S10). RESULTS: The total ultrafiltration volume was similar between HD and IUF (HD 2.5 ± 0.3 vs. ICF 2.1 ± 0.3 L/session, p = 0.196). The reduction rate of ECW was significantly higher than that of intracellular water (ICW) after HD (ECW -7.9% ± 0.8% vs. ICW -3.0% ± 0.9%, p < 0.001) and IUF (ECW -5.8% ± 0.9% vs. ICW -3.6% ± 0.8%, p = 0.048). However, the change in the ratio of ECW to total body water in HD was significantly larger than that in IUF (HD -3.2% ± 0.3% vs. ICF -1.1% ± 0.4%, p < 0.001). The reduction rates in serum tonicity (effective osmolality) were higher after HD than after IUF (HD -1.8% ± 0.5% vs. IUF -0.6% ± 0.2%, p = 0.052). Among the components of effective osmolality, the reduction rates of serum K+ and glucose levels after HD were significantly higher than those after IUF (serum K+: HD -30.5% ± 1.6% vs. IUF -0.5% ± 3.8%, p < 0.001; serum glucose: HD -15.4% ± 5.0% vs. IUF 0.7% ± 4.8%, p = 0.026), while the serum Na+ level was slightly and similarly reduced (HD -0.8% ± 0.4% vs. IUF -0.8% ± 0.4%, p = 0.500). The reduction in the osmolal gap value (measured osmolality-calculated osmolarity) was significantly greater after HD sessions than after IUF sessions (HD -12.4 ± 1.4 vs. IUF 2.0 ± 1.0 mOsm/kg, p = 0.001). CONCLUSION: The extracellular fluid reduction effect of HD is stronger than that of IUF. The different changes in effective osmolality and osmolal gap after HD and IUF sessions may be related to the different effects of HD and IUF on fluid distribution.

Osmolal and anion gaps after acute self-poisoning with agricultural formulations of the organophosphorus insecticides profenofos and diazinon: A pilot study.

Self-poisoning with organophosphorus (OP) insecticides is an important means of global self-harm. The insecticides are formulated with solvents that may also contribute to toxicity. We set up a study to detect changes in osmolal and anion gaps following ingestion of OP insecticides. We recruited consecutive patients admitted to a Teaching Hospital, Sri Lanka, with a history of OP self-poisoning. The osmolal and anion gaps were calculated on admission and at 4, 24 and 72 h post-ingestion together with ethanol concentration. Forty-nine patients were recruited (28 profenofos, 10 diazinon, one coumaphos, one chlorpyrifos, one phenthoate and eight unknown OP). Only modest increases in osmolal and anion gaps were noted. Small rises in osmolal gap above the upper limit of normal were noted in 16/49 (32.7%) of all cases, 9/28 (32.1%) profenofos cases and 4/10 (40.0%) diazinon cases. The anion gap was raised in 24/49 (49.0%) of all cases, 15/28 (53.6%) profenofos cases and 5/10 (50.0%) diazinon cases. We observed a trend for a fall in osmolal gap during the first 24 h, followed by an increase up to 72 h. There was no correlation between the anion gap and serum lactate concentration, indicating that a lactic acidosis was not responsible for the anion gap. Formate, which could have explained the increased gap, was not detected in any of the samples; ketoacids (beta-hydroxybutyrate and acetoacetate) were not measured. This pilot study found that profenofos and diazinon poisoning caused only modest increases in the osmolal and anion gaps in a minority of cases.

The Role of the Nephrologist in Management of Poisoning and Intoxication: Core Curriculum 2022.

Poisoning is a common problem in the United States. Acid-base disturbances, electrolyte derangements, or acute kidney injury result from severe poisoning from toxic alcohols, salicylates, metformin, and acetaminophen. Lithium is highly sensitive to small changes in kidney function. These poisonings and drug overdoses often require the nephrologist's expertise in diagnosis and treatment, which may require correction of acidosis, administration of selective enzyme inhibitors, or timely hemodialysis. The clinical and laboratory abnormalities associated with the poisonings and drug overdoses can develop rapidly and lead to severe cellular dysfunction and death. Understanding the pathophysiology of the disturbances and their clinical and laboratory findings is essential for the nephrologist to rapidly recognize the poisonings and establish an effective treatment plan. This installment of AJKD's Core Curriculum in Nephrology presents illustrative cases of individual poisonings and drug overdoses and summarizes up to date information on their prevalence, clinical and laboratory findings, pathophysiology, diagnosis, and treatment.

Intoxication by Hand-Sanitizers and other Toxic Alcohols in a Low-Resource Setting: Two Case Reports.

Toxic alcohol poisoning can be lethal if not identified early and treated appropriately. Toxic alcohol assays are often unavailable in low-resource setting, so clinicians have to infer a diagnosis based on suspicion, repeated evaluation and biochemical course. We report a case of toxic alcohol poisoning concealed by auto-intoxication with in-hospital hand sanitizer. The eventual appearance of a concurrent high anion gap prompted dialysis. In another case, a comatose patient presented with a high osmolal gap and a high anion gap. Incorrect a priori opinions caused us to defer dialysis and the patient died shortly afterwards. Clinicians should be aware that toxic alcohol poisoning can produce a confusing diagnostic picture with an insidious course, and that doctor delay can prove fatal. LEARNING POINTS: Toxic alcohol ingestion may be lethal and warrants early identification, but this is not always possible.Incorrect a priori opinions by clinicians, or the co-ingestion of other alcohols by a patient, may produce a confusing diagnostic picture.Physicians should not defer immediate treatment for patients suspected of toxic alcohol ingestion with a double gap or visual disturbances.

Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021.

The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful calculation that divides the metabolic acidoses into 2 categories: high AG metabolic acidosis (HAGMA) and hyperchloremic metabolic acidosis-and thereby delimits the potential etiologies of the disorder. When the [AG] is compared with changes in the bicarbonate concentration, other occult acid-base disorders can be identified. Furthermore, finding that the AG is very small or negative can suggest several occult clinical disorders or raise the possibility of electrolyte measurement artifacts. In this installment of AJKD's Core Curriculum in Nephrology, we discuss cases that represent several very common and several rare causes of HAGMA. These case scenarios highlight how the AG can provide vital clues that direct the clinician toward the correct diagnosis. We also show how to calculate and, if necessary, correct the AG for hypoalbuminemia and severe hyperglycemia. Plasma osmolality and osmolal gap calculations are described and when used together with the AG guide appropriate clinical decision making.

Assessing urine ammonium concentration by urine osmolal gap in chronic kidney disease.

Acidemia is one of the risk factors for end-stage kidney disease and increases the mortality rate of patients with chronic kidney disease (CKD). Although urinary ammonium (U-NH4 + ) is the crucial component of renal acid excretion, U-NH4 + concentration is not routinely measured. To estimate U-NH4 + , urine osmolal gap (UOG = urine osmolality - [2(Na+ + K+ ) + urea + glucose]) is calculated and the formula (U-NH4 +  = UOG/2) has traditionally been used. However, the usefulness of this formula is controversial in CKD patients. We assessed the relationship between U-NH4 + and UOG in patients with CKD. Blood and spot urine samples were collected in 36 patients who had non-dialysis-dependent CKD. The mean ± SD age of patients was 72.0 ± 14.8 years, and the mean ± SD serum creatinine and U-NH4 + were 2.7 ± 2.3 mg/dl and 9.3 ± 9.2 mmol/L, respectively. A significant relationship was found between UOG/2 and U-NH4 + (r = .925, p < .0001). U-NH4 + estimated using the UOG was on average higher by 4.7 mmol/L than the measured one. Our results suggested that UOG could be a useful tool in clinical settings, especially in patients with moderate to severe CKD.

Metabolic acidosis due to ingestion of lanthanum sulfates and chlorides in cetyl alcohol solution pool cleaner.

Cetyl Alcohol is a rare cause of acidosis if ingested in large quantities. Hyponatremia with overlapping anion gap and osmolal gap-positive metabolic acidosis may appear to have iso-osmolar serum. This is a case of an unusual toxic exposure.

Critical evaluation of equations for serum osmolality: Proposals for effective clinical utility.

BACKGROUND: Many studies have assessed the predictive accuracy of serum osmolality equations. Different approaches for selecting a usable equation were compared using thirty published equations and patient data from a regional hospital laboratory. METHODS: Laboratory records were extracted with same-sample results for measured serum osmolality, sodium, potassium, urea and glucose analysed in a regional hospital laboratory between 1/1/2017-31/12/2018. Differences were analysed using Passing-Bablok and difference (Bland-Altman) analysis. Three approaches were compared: the shotgun approach, adjusting for bias, and deriving a novel equation using multivariate analysis. The criteria for success included bias ≤0.7%, a 230 - 400 mOsm/kg range, and osmolal gap (OG) 95% reference limits within ±10 mOsm/kg. RESULTS: The majority of equations produced proportionally negative-biased results. The shotgun approach identified two equations (EQ19, EQ6) with bias ≤0.7% but unworkable OG reference limits. The bias adjustment approach produced several equations with bias ≤ 0.7% and OG reference limits within or equivalent to ±10 mOsm/kg. A novel equation generated by us (1.89Na+ + 1.71 K+ + 1.08 Urea + 1.08 Glucose + 13.7) improved with the adjustment of bias and was not superior to the adjusted published equations. CONCLUSION: Few published equations are immediately usable. Adjustment of bias derives several usable equations of which the best had OG ranges <20 mOsm/kg. We conclude that adjustment of bias can generate equations of equal or superior performance to that of novel equations.

Comparison of measured and calculated osmolality levels.

BACKGROUND: Serum osmolality levels are measured to determine acid-base and electrolyte imbalance in serum. In cases where measurement is not possible, the serum osmolality value can be calculated by various calculation methods. In this study, we compared the Worthley osmolality calculation method which is used most frequently mentioned in literature and the measurements made with vapor pressure osmometer used in our laboratory. We compared whether there was a difference between the results obtained by measurement and calculation method in different age groups. METHODS: 221 serum samples of patients who were admitted to the Eskisehir Osmangazi University Hospital Biochemistry Laboratory between December 2016 and May 2018 were included in this study. Glucose, blood urea nitrogen and sodium values were recorded to determine the calculated osmolality values of the patients. RESULTS: There was a statistically significant difference between the measured osmolality values and the calculated osmolality values of the patients (p < 0.001). When compared according to age groups, there was a significant difference between calculated osmolality values (p = 0.006), but there was no difference in measured osmolality values (p = 0.787) in different age groups. It has been observed that this difference in the calculated osmolality values between the age groups is derived from the adult group (18-65, p < 0.001). CONCLUSION: Our results showed that it is not reliable to calculate serum osmolality values, especially in the adult age group. According to our results the calculated osmolality values are higher than our measured osmolality values.

Ethylene Glycol Poisoning with a Near-Normal Osmolal Gap: A Diagnostic Challenge.

Ethylene glycol is a colorless, odorless, sweet-tasting liquid commonly found in antifreeze, as well as in industrial agents. It is regarded as one of the toxic alcohols. Ethylene glycol poisoning usually occurs due to ingestion, and its toxicity is mediated by its metabolites, glycolic acid, and oxalate. These metabolites can cause neurological symptoms, gastrointestinal symptoms, and/or renal failure if not diagnosed and treated promptly. The diagnosis can be very challenging as the test used to detect ethylene glycol in the blood may not be readily available or due to an inaccurate history. The treatment of ethylene glycol poisoning consists of supportive care, sodium bicarbonate, and the use of an antidote (ethanol or fomepizole) which inhibits alcohol dehydrogenase and thereby prevents the formation of toxic metabolites. Patients with advanced poisonings may also require dialysis. The diagnosis is usually suggested by a high anion gap metabolic acidosis and an elevated osmolal gap in the setting of a suspected ingestion. Rarely, the osmolal gap may be close to normal which can delay the diagnosis or lead to a misdiagnosis. We report a case of ethylene glycol ingestion with a near-normal osmolal gap.

[A Sweet Drink with Consequences]. / Ein süsser Drink mit Folgen.

A Sweet Drink with Consequences Abstract. Intoxications with ethylene glycol are rare, however, small quantities from the substance can be life-threatening. Regarding the treatment it is important to recognize the intoxication quickly and to immediately start the appropriate treatment. Intoxications with ethylene glycol or with methanol should always be considered as differential diagnosis in patients with severe metabolic acidosis. It is also very important to calculate the osmolal gap.

Ethylene Glycol Toxicity in the Setting of Recurrent Ingestion: A Case Report and Literature Review.

Ethylene glycol (EG) poisoning is a toxicologic emergency requiring high clinical suspicion and early diagnosis to prevent life-threatening complications. Direct EG quantification methods involve cumbersome and time-consuming laboratory tests of limited utility in the emergency setting. Accordingly, the osmolal gap is frequently employed as a surrogate screening method in cases of suspected toxic alcohol poisoning. However, the osmolal gap has several inherent limitations to be considered when used as a diagnostic tool for EG toxicity. Although many of these limitations are widely acknowledged, the clinical finding of a normal serum osmolal gap in the setting of recurrent toxic alcohol exposure is an observation that has remained largely unexplored. The purpose of this case report is to characterize the accelerated osmolal gap to anion gap conversion that may occur in the setting of chronic toxic alcohol abuse.

The role of the clinical laboratory in diagnosing acid-base disorders.

Acid-base homeostasis is fundamental for life. The body is exceptionally sensitive to changes in pH, and as a result, potent mechanisms exist to regulate the body's acid-base balance to maintain it in a very narrow range. Accurate and timely interpretation of an acid-base disorder can be lifesaving but establishing a correct diagnosis may be challenging. The underlying cause of the acid-base disorder is generally responsible for a patient's signs and symptoms, but laboratory results and their integration into the clinical picture is crucial. Important acid-base parameters are often available within minutes in the acute hospital care setting, and with basic knowledge it should be easy to establish the diagnosis with a stepwise approach. Unfortunately, many caveats exist, beginning in the pre-analytical phase. In the post-analytical phase, studies on the arterial reference pH are scarce and therefore many different reference values are used in the literature without any solid evidence. The prediction models that are currently used to assess the acid-base status are approximations that are mostly based on older studies with several limitations. The two most commonly used methods are the physiological method and the base excess method, both easy to use. The secondary response equations in the base excess method are the most convenient. Evaluation of acid-base disorders should always include the assessment of electrolytes and the anion gap. A major limitation of the current acid-base laboratory tests available is the lack of rapid point-of-care laboratory tests to diagnose intoxications with toxic alcohols. These intoxications can be fatal if not recognized and treated within minutes to hours. The surrogate use of the osmolal gap is often an inadequate substitute in this respect. This article reviews the role of the clinical laboratory to evaluate acid-base disorders.