Unexpectedly Abnormal Electrolytes in a 60 Year Old Man with Dementia

Patient History

A 60 year old man with pre-existing dementia presented to the emergency department (ED) with mental confusion and signs of dehydration. He had been found awake on the floor in his home and had not been eating or drinking well for several days. His vital signs and physical exam were generally normal (temperature: 36.5°C; blood pressure: 115/81 mmHg; pulse: 69/min; respiratory rate: 18/min; oxygen saturation: 99% on room air) apart from apparent delirium, dry mucous membranes/mouth, and an involuntary jerking of the upper extremities. The ED personnel sent blood specimens to the laboratory for STAT chemistry and hematology tests.

Initial laboratory results revealed markedly elevated sodium and chloride, with both analyte concentrations above their respective reportable range. The medical laboratory scientist reviewing the results considered the specimen potentially contaminated with saline or another intravenous (IV) fluid. She rejected the specimen and requested a re-collection; however, upon receipt of a second and ultimately a third specimen, each set of results was found consistent with the original. The attending physician then requested whole blood sodium measured using a point-of-care device. This result was consistent with those of the main laboratory, with a value >180 mmol/L. Based on this comparison and in consultation with the laboratory medical director, the attending physician deemed the results of all collections to be relevant to the patient’s condition. The elevated sodium on the final specimen was identified as a critical value and was appropriately annotated in the hospital information system. Select laboratory values associated with the encounter, including the repeat collections, are presented in Table 1. The patient was diagnosed with severe hypernatremia resulting from dehydration, leading to hypernatremic encephalopathy and acute kidney injury (AKI). He was admitted to the hospital and underwent extensive fluid replacement (Ringer’s lactate, 5% dextrose) with gradual resolution of electrolyte balance, neurological function, and AKI over the next 7 days, after which he was discharged.

Dehydration

Dehydration is generally defined as the excessive loss of body water.^1,2 It is the most common cause of fluid and electrolyte imbalance in older adults and contributes a heavy burden to the medical system in the United States, with more than $5.5 billion spent on related hospital admissions annually.^2,3 Dehydration is categorized into groups based on the final extracellular osmolality within the affected patient (Table 2). Distinguishing the etiology and category of dehydration present is critical because these aspects define clinical management of the condition.²

Older adults are at increased risk for dehydration because of numerous changes in physiology associated with the aging process. For example, as patients age, they may experience decreases in thirst sensation (hypodipsia), a general decline in renal function, decreased activity of the renin-angiotensin system, and changes in renal sensitivity to vasopressin.^2,4 Moreover, aging may affect normal physiological adaptations to volume depletion, including neurohumoral control of blood pressure and cardiovascular responses to changes in blood volume. Enhancing this risk are various pathologic and pharmacologic etiologies that are more common in these age groups, including changes in functional and mental status, reduced mobility, and comorbidities that require pharmacological intervention such as the use of diuretics or laxatives.²

Electrolyte Abnormalities

The patient described in this case study presented with hypertonic dehydration that resulted in electrolyte abnormalities most notable for hypernatremia and hyperchloremia. In most patients with hypertonic dehydration, clinical presentation is influenced most prominently by the concentration of extracellular sodium; the effects of other constituents are less pronounced or overshadowed by the severity of the sodium disturbance.^2,5 Signs and symptoms observed in hypernatremia are outlined in Table 3.

Hypernatremia is defined as a serum sodium concentration that exceeds ~145 to 150 mmol/L.^6,7 It is most commonly caused by a net water loss from the body as described above; however, pathologic changes may occur as a result of any number of conditions that involve the loss of fluid and/or the gain of sodium (Table 4). Those at the highest risk of net water-loss hypernatremia include infants, older adults, and patients with mental impairment.⁶ In adults, symptoms are relatively mild until values exceed 160 mmol/L. In patients with the most severe cases, hypernatremia results in significant fluid redistribution within the central nervous system, leading to encephalopathy and altered mental status as observed in this patient.^7,8

In contrast, hyperchloremia is considered a serum chloride that exceeds ~108 mmol/L.⁵ Because chloride is the primary anion in the body, conditions that cause hypernatremia often lead to concurrent hyperchloremia. However, independent increases in chloride, when encountered, are associated with various physiological effects, including hyperchloremic metabolic acidosis, gastrointestinal symptoms, and impairment of renal function.⁹ Chloremic excess may be observed in patients receiving aggressive treatment with normal saline (0.9% NaCl) because of its relatively high chloride content in contrast to normal physiological levels (serum: ~100 mmol/L; 0.9% saline: 154 mmol/L). In addition, chloride may be elevated in some patients with respiratory alkalosis, in whom the renal retention of chloride offsets the loss of bicarbonate.⁵

Laboratory Assessment

In this case study, severe hypernatremia and hyperchloremia presented an interpretive challenge to the laboratory scientist on duty. Many laboratory professionals can certainly attest that in isolation, it is difficult at times to recognize that exceptionally abnormal laboratory values can reflect both clinical reality and error. In this instance, although the electrolyte values may have been surprising, they were accompanied with other results that were not consistent with dilutional contamination by saline or other IV fluids (eg, the elevated urea nitrogen and creatinine).

Clinicians routinely use IV fluids for the repletion, maintenance, or selective movement of ions, metabolites, and water throughout the body. They may be isotonic, hypertonic, or hypotonic in nature and are generally classified as crystalloid or colloid.^10-12 Isotonic solutions are employed to maintain hydration or replete lost intravascular fluid (eg, because of blood loss or routine dehydration, or during surgery). In contrast, hypotonic solutions replete lost intracellular fluids in tissue (eg, in hyperosmolar states) and hypertonic solutions replace deficient ions and draw interstitial fluids back into the vascular space (eg, with edema).¹² Crystalloid fluids consist of small molecules and ions that easily diffuse across capillary membranes, moving from the vascular space into the tissues. Common constituents of these fluids include sodium, chloride, potassium, calcium, lactate, and glucose. Examples of crystalloid fluids and their uses are outlined in Table 5. Colloid fluids contain larger molecules that do not easily pass through the capillary membrane, contributing direct vascular volume and drawing fluid from the interstitium into the intravascular space. Common constituents of colloid fluids include albumin, hydroxyethyl starch, and various forms of gelatin. Because of recent evidence suggesting that colloid solutions may contribute to patient harm, crystalloid IV fluid usage is more common.¹¹

In our experience, specimen contamination is most often observed (or recognized) when there is contamination with crystalloid fluids, where marked changes in electrolytes, glucose, or other small molecules are easily noted. The complexities involved are considerable because the baseline values of the patient, fluid constituents, and sheer displacement volume in a collected specimen combine to have a significant effect on laboratory results.^13,14 For example, contamination with isotonic (0.9%) saline (NaCl) or Ringer’s lactate solution has a relatively mild effect on patient sodium and chloride until the displacement volume is extensive; however, notable decreases in other analytes (eg, calcium, total protein) may be observed earlier (see Figure 1A and 1B).¹⁵ In contrast, contamination with small amounts of highly concentrated solutions (eg, 5% dextrose, hypertonic (3%) saline) can lead to marked deviations in analyte concentration with little dilutional effect on other analytes. Using this type of information, some authors have proposed methods to detect potentially contaminated specimens using direct cut points (eg, Na⁺: >180 mmol/L paired with K⁺ <2.5 mmol/L) and statistically guided algorithms.^16-18

Case Resolution

The events that occurred in the laboratory were investigated, and in-services were provided to instruct laboratory staff on the evaluation of chemistry results in the context of potential contamination. In this case, the patient presented with markedly abnormal sodium and chloride; however, the remainder of the analytes were normal, near normal, or even elevated, reflecting a true pathologic condition. In particular, the patient’s urea nitrogen and creatinine were elevated, suggesting that the results were accurate. As part of the educational process, involved staff performed dilution studies and estimated the calculated effects of commonly administered fluids on laboratory values in heparinized whole blood. These studies provided a reference point that staff could employ in deciphering dilutional patterns that might be observed in true contamination (see Figure 1A and 1B). Moreover, we proposed the following general guidelines for the staff:

1. Evaluate the entire picture of laboratory results; do not focus on 1 or 2 greatly abnormal values.

2. Review for markedly or inappropriately decreased results, considering that although the intent of infusions is to correct/normalize certain blood constituents, solutions free of an analyte will artificially decrease other values quickly.

3. Use automated flagging algorithms such as delta checks or contamination sentinel rules (eg, those of Hernandez¹⁶) to assist in identifying abnormalities.

4. If possible, correlate results with other departments. For example, a marked shift in a patient’s mean corpuscular volume without recent transfusion may support an abnormally hyper- or hypotonic condition.^19,20

5. Use available resources, such as a review of patient charts or contacting the patient’s clinician or nurse directly.

6. When all else fails, ask for help. Contact a supervisor or the laboratory medical director for assistance. Unilateral decisions to reject potentially contaminated specimens can lead to complaints, delays to patient care, and even patient harm.²¹

The assessment of potentially contaminated specimens can be complex; however, following the above suggestions is likely to assist most laboratory staff in dealing with situations such as that described in this case study in their day-to-day work.

Abbreviations

Abbreviations
 
• ED

  emergency department

 
• IV

  intravenous

 
• AKI

  acute kidney injury

References