Index
A common electrolyte problem is strictly defined as a hyperosmolar condition caused by decreased total body water.
This decrease in water is related to the electrolyte content. Hypernatremia is a “water problem,” not a problem of sodium homeostasis.
Patients who develop hypernatremia outside the hospital are usually older people with mental and physical disabilities, often with an acute infection.
Those who develop hypernatremia during hospitalization have an age distribution similar to the general hospital population.
In both patients, hypernatremia is caused by a lack of thirst and restricted access to water, often exacerbated by pathological conditions with increased fluid loss.
The development of hyperosmolality from water loss can reduce neuronal cells and the resulting brain injury. The loss of volume can cause circulatory problems (e.g., tachycardia, hypotension).
Rapid replacement of free water can cause cerebral edema. Hypernatremia occurs when there is a net loss of water or again in sodium, and it reflects very little water relative to the body’s total sodium and potassium.
In a simplified view, the serum sodium concentration (Na +) can be seen as a function of the total interchangeable sodium and potassium in the body and total body water. The formula is expressed below:
- Na + = Na + total body + K + total body / total body water.
As a result, hypernatremia can only develop due to a loss of free water or again in sodium or a combination of both. Hypernatremia, by definition, is a state of hyperosmolality because sodium is the dominant extracellular cation and solute.
Normal plasma osmolality (Posm) is between 275 and 290 mOsm / kg and is determined mainly by the concentration of sodium salts. (Calculated plasma osmolality: 2 (Na) mEq / L + serum glucose (mg / dL) / 18 + BUN (mg / dL) /2.8).
The regulation of the Post and the plasma concentration of sodium is mediated by changes in water intake and water excretion. This occurs through two mechanisms:
- Urinary concentration (through the pituitary secretion and the renal effects of the antidiuretic hormone arginine vasopressin).
- However.
In a healthy individual, thirst and release of arginine vasopressin antidiuretic are stimulated by an increase in the osmolality of bodily fluids above a certain osmotic threshold, which is approximately 280-290 mOsm / L and is considered similar if not identical to thirst as for the release of antidiuretic arginine vasopressin.
An increase in osmolality attracts water from the cells to the blood, dehydrating specific neurons in the brain that serve as osmoreceptors or ” tonicity receptors. ” It is postulated that the deformation of the size of the neuron activates these cells (thus acting as mechanoreceptors).
In stimulation, they point to other brain parts to initiate thirst and AVP release, resulting in increased water intake and urinary concentration, rapidly correcting the hypernatremic state.
Urinary concentration – Antidiuretic Arginine Vasopressin and kidney
The conservation and excretion of water by the kidney depends on the normal secretion and action of AVP and is highly regulated.
The stimulus for the secretion of antidiuretic arginine vasopressin is the activation of hypothalamic osmoreceptors, which occurs when plasma osmolality reaches a certain threshold (approximately 280 mOsm / kg).
At plasma osmolalities below this threshold level, the secretion of AVP is suppressed at low or undetectable levels.
Other afferent stimuli, such as a decrease in the adequate volume of arterial blood, pain, nausea, anxiety, and numerous medications, can also cause a release of antidiuretic arginine vasopressin.
The antidiuretic arginine vasopressin is synthesized in specialized magnocellular neurons whose cell bodies are located in the supraoptic and paraventricular nuclei of the hypothalamus.
The prohormone is processed and transported by the axon, ending in the posterior pituitary gland. It is secreted as an active AVP hormone in the circulation in response to an appropriate stimulus (hyperosmolality, hypovolemia).
Antidiuretic arginine vasopressin binds to the V2 receptor located in the basolateral membrane of the primary cells of the renal collecting ducts.
The binding to this receptor coupled to protein G initiates a cascade of signal transduction that leads to the phosphorylation of aquaporin two and its translocation and insertion in the apical (luminal) membrane, creating “water channels” that allow the absorption of free water, in this case, a waterproof segment of the tubular system.
However,
Thirst is the body’s mechanism for increasing water consumption in response to deficits detected in body fluids. As with the secretion of antidiuretic arginine vasopressin, thirst is mediated by an increase in effective plasma osmolality of only 2-3%.
It is believed that thirst is mediated by osmoreceptors located in the anteroventral hypothalamus. The osmotic sediment threshold averages approximately 288-295 mOsm / kg.
This mechanism is so effective that patients can not concentrate their urine (diabetes insipidus) even in pathological states and excrete excessive amounts of urine (10-15L / d).
Hypernatremia does not develop because thirst is stimulated, and the osmolality of the body fluid is maintained at the expense of deep secondary polydipsia.
Hypernatremia development is virtually impossible if the thirst response is intact and the water available.
Therefore, sustained hypernatremia can occur only when the thirst mechanism is altered and water intake does not increase in response to hyperosmolality or when water intake is restricted.
Significant hypovolemia stimulates the secretion of antidiuretic arginine vasopressin and thirst. The decrease in blood pressure of 20-30% results in levels of antidiuretic arginine vasopressin many times higher than those required for maximum antidiuresis.
Hypernatremic states can be classified as isolated water deficits (usually not associated with intravascular volume changes), hypotonic fluid deficits, and hypertonic sodium gain.
Regulation of the Volume of the Brain Cell
Acute hypernatremia is associated with a rapid decrease in intracellular water content and brain volume caused by an osmotic displacement of the free water from the cells.
Within 24 hours, the uptake of electrolytes in the intracellular compartment results in partial restoration of brain volume.
The second phase of adaptation, characterized by an increase in the content of intracellular organic solute (accumulation of amino acids, polyols, and methylamines), restores brain volume to normal.
Some patients complete this adaptive response in less than 48 hours. The accumulation of intracellular solutes carries the risk of cerebral edema during rehydration. The response of brain cells to hypernatremia is critical.
Epidemiology and Frequency
A retrospective study of a single center in Europe, which included 981 patients, found a 9% incidence of hypernatremia in the intensive care unit.
However, it was also found that only 23% already had the condition among patients with hypernatremia when they entered the intensive care unit.
A Canadian study of 8,000 adult patients identified acquired hyponatremia in the intensive care unit in 11% and hypernatremia caught in the intensive care unit in 26% of these patients.
The report found that the mortality rate in patients with hyponatremia or hypernatremia acquired in the intensive care unit was higher than that of the patients in the study with normal serum sodium levels, being 28% versus 16%, p <0.001 and 34% versus 16%, p <0.001, respectively.
Morbidity
Mortality rates of 30-48% have been demonstrated in patients in the intensive care unit with serum sodium levels above 150 mmol / l.
A review of 256 patients who attended a Turkish emergency department with severe hypernatremia (serum sodium> 160mmol / l) determined that the following factors were independently associated with mortality:
- Low systolic blood pressure
- Low PH
- Sodium sodium> 166 mmol / L.
- Increase in plasma osmolarity.
- The average sodium reduction rate of 0.134 mmol / L / h or less.
- Dehydration
- Pneumonia.
Darmon et al. sought to determine the prevalence of acquired hypernatremia in the ICU and if this condition could affect patient outcomes.
Of 8140 patients reviewed in the retrospective study, 1245 had acquired hypernatremia in the intensive care unit (defined in the survey as acquired hypernatremia 24 hours or more after admission to the intensive care unit).
This included 901 patients (11.1%) with mild hypernatremia and 344 (4.2%) with moderate to severe hypernatremia.
I compared the hospital mortality rates for patients without hypernatremia with cohort members with the condition.
The authors determined that the risk ratio of subdistribution for mortality due to acquired hypernatremia in the intensive care unit was 2.03 for the mild form of the condition and 2.67 for moderate to severe hypernatremia.
However, whether the association of hypernatremia acquired in the intensive care unit with an increased risk of death reflects a direct effect of hypernatremia is uncertain or is a marker of suboptimal quality of care.
One study confirmed that the maximum daily sodium is a significant risk factor for developing acute kidney injury in patients with subarachnoid hemorrhage (SAH) receiving hypertonic saline therapy.
This therapy is often used to control intracranial hypertension and control symptomatic hyponatremia.
Of 736 patients in one study, 9% (64) developed acute kidney injury. For each increase of 1 mEq / L in the maximum daily rate of serum sodium, the risk of developing acute kidney injury increased by 5.4%. The risk of death was more than double in patients who developed acute kidney injury.
It has been found that hypernatremia acquired early in the intensive care unit is a frequent complication in patients with severe sepsis and is associated with the volume of 0.9% saline solution received during the first 48 hours of admission to the intensive care unit.
Of 95 patients with severe sepsis, 29 (31%) developed hypernatremia in 5 days in one study. For every 50 ml/kg increase in 0.9% saline intake during the first 48 hours, the odds of hypernatraemia increased by 1.61 times.
The patients who developed hypernatremia had a longer duration of mechanical ventilation and higher mortality.
According to Leung et al., preoperative hypernatremia is associated with increased perioperative morbidity and mortality at 30 days. In their study, 20,029 patients with preoperative hypernatremia (> 144 mmol / l) were compared with 888,840 patients with a normal basal sodium (135-144 mmol / l).
The morbidity and mortality probabilities increased according to the severity of the hypernatremia (p <0.001 for the comparison in pairs for mild categories [145-148 mmol / l] as opposed to severe [> 148 mmol / l]).
Hypernatremia, versus normal basal sodium, was associated with a higher probability of perioperative major coronary events (1.6% vs. 0.7%), pneumonia (3.4% vs. 1.5%), and venous thromboembolism (1, 8% vs. 0.9%).
Age
The groups most commonly affected by hypernatremia are older adults and children. Neonatal hypernatremia associated with breastfeeding has been recognized in infants ≤21 days of age who have lost ≥10% of birth weight.
Medical care
The objectives of treatment in hypernatremia are the following:
- Recognition of symptoms when present.
- Identification of the underlying cause (s).
- Correction of volume disturbances.
- Hypertonicity correction.
The correction of hypertonicity requires a careful reduction of the serum and serum osmolality with the replacement of free water, either orally or parenterally. The rate of sodium correction depends on how acutely the hypernatremia developed and the severity of the symptoms.
Acute symptomatic hypernatremia, defined as hypernatremia that occurs in a documented period of fewer than 24 hours, should be corrected quickly. However, chronic hypernatremia (> 48 h) should be updated more slowly due to the risks of cerebral edema during treatment.
The brain adapts and mitigates chronic hypernatremia by increasing the intracellular content of organic osmolytes. If the extracellular tonicity decreases rapidly, the water will move to the brain cells, producing cerebral edema, which can cause a hernia, permanent neurological deficits, and myolysis.
Treatment Recommendations for Symptomatic Hypernatremia
The recommendations are the following:
- Establish documented start (acute, <24 h, chronic,> 24 h).
- In acute hypernatremia, correct serum sodium at an initial rate of 2-3 mEq / L / h (for 2-3 h) (maximum total, 12 mEq / L / d).
- Measure the electrolytes in serum and urine every 1-2 hours.
- Perform serial neurological exams and decrease the correction rate with improved symptoms.
- Chronic hypernatremia without symptoms or mild symptoms should be corrected at a rate not exceeding 0.5 mEq / L / h and 8-10 mEq / d (for example, 160 mEq / L at 152 mEq / L in 24 h).
- If there is a volume deficit and hypernatremia, the intravascular volume should be restored with isotonic sodium chloride before administering free water.
Estimation of the Replacement Fluid
Total body water refers to the patient’s lean body weight (the percentage of TBW decreases in patients with morbid obesity). The entire body water deficit in the hyperosmolar patient that needs to be replaced can be estimated approximately using the following formula:
- TBW deficit = correction factor x pre-borbot weight x (1 – 140 / Na +)
Straight losses (insensitive, renal) should be added.
However, the following formulas from Adrogué-Madias, are preferable to the conventional equation for water deficit because the above equation underestimates the deficit in patients with hypotonic fluid loss and is not helpful in situations where sodium should be used and potassium.
The formulas used to control hypernatremia are detailed below:
Equation 1:
- TBW = weight (kg) x correction factor
The correction factors are the following:
- Children: 0.6
- Non-elderly men: 0.6
- Non-elderly women: 0.5
- Elderly men: 0.5
- Elderly women: 0.45
Equation 2:
- change in serum Na + = (infusion Na + – serum Na +) ÷ (total body water + 1)
Equation 3:
- change in serum Na + = ([infusion Na + + infusion K +] – serum Na +) ÷ (TBW + 1)
Equation 2 allows the estimation of 1 L of any infusion in the serum Na + concentration. Equation 3 allows the analysis of 1 L of any information containing Na + and K + in Na + serum.
Common infusions and their Na + contents include the following:
- 5% dextrose in water (D 5 W): 0 mmol / L.
- 0.2% sodium chloride in 5% dextrose in water (D 5 2NS): 34 mmol / L.
- 45% sodium chloride in water (0.45NS): 77 mmol / L.
- Ringer’s lactate solution: 130 mmol / L.
- 0.9% sodium chloride in water (0.9NS): 154 mmol / L.
An example of the above calculations is the following: an 80-year-old obtuse man is taken to the emergency room with dry mucous membranes, fever, tachypnea, and blood pressure of 134/75 mm Hg.
Its serum sodium concentration is 165 mmol / L. He weighs 70 kg. This man has hypernatremia due to the insensible loss of water. The TBW of the man is calculated as follows:
- (0.5 x 70) = 35 L
To reduce the serum sodium of man, D5 W will be used. Therefore, the retention of 1 L of D5 W will reduce its serum sodium by (0 – 165) ÷ (35 + 1) = -4.6 mmol. The goal is to reduce your serum sodium by ten mmol / L in 24 hours.
Therefore, it is required (10 ÷ 4.6) = 2.17 L of solution. About 1-1.5 L for mandatory water loss will be added to obtain up to 3.67 L of D5 W for 24 hours, or 153 cc / h.
A clinically meaningful study by Lindner and his colleagues found that all of the above formulas correlated significantly with the changes measured in serum sodium in the patient cohort as a whole, but the individual variations were extreme.
Therefore, although the above formulas can guide therapy, serial serum sodium measurements are prudent. This finding is not surprising, considering that the interindividual variables make it difficult to estimate accurate individual total body water and its distribution in different body compartments.
For example, the degree to which interindividual differences in the percentage of body fat affect total body water is considerable.
Other Treatment Considerations
If hypernatremia is accompanied by hyperglycemia with diabetes, be careful when using a replacement fluid that contains glucose. However, the proper use of insulin will help during the correction.
In hypervolaemic and hypernatremic patients in the intensive care unit who have altered renal sodium and potassium excretion (e.g., after renal failure), adding a loop diuretic to free water boluses increases renal excretion of sodium.
The loss of fluid during therapy with loop diuretics should be restored with the administration of a hypotonic fluid for urine.
The use of thiazide diuretics to improve sodium excretion has been suggested as a treatment for acquired hypernatremia in the intensive care unit.
However, a randomized, placebo-controlled trial in 50 intensive care unit patients found that hydrochlorothiazide, 25 mg/day for up to 7 days, did not significantly affect the serum or urinary sodium concentration.
Hypernatremia in situations of volume overload (e.g., heart failure and pulmonary edema) may require dialysis for correction.
Although oral and parenteral routes can replace water, an obtuse patient with a large free water deficit probably requires parenteral treatment. If the debt is small and the patient is alert and oriented, verbal correction may be preferred.
Once hypernatremia is corrected, efforts are directed at treating the condition’s underlying cause. Such measures may include free access to water and better control of diabetes mellitus.
In addition, the correction of hypokalemia and hypercalcemia as etiologies for nephrogenic diabetes insipidus may be necessary. Vasopressin (AVP, DDAVP) should be used to treat central diabetes insipidus.
