Infants and children differ from mature adults in their metabolic requirements and turnover, composition of body fluids, and the degree to which regulation and/or adaptation occurs in normal or disordered states. All of these factors not only affect the growth and development of a child, but also, if deranged, may result in significant morbidity and mortality. Hence, a clear understanding of the composition of body fluids and their constituents in different compartments is essential to the optimal management in all children. Moreover, a disturbance in fluid, electrolyte, and/or acid-base balance commonly accompanies many other disorders. Thus, a pediatrician must be able to diagnose and appropriately manage such disturbances.
BODY FLUID AND ELECTROLYTE DISTRIBUTION AND REGULATION
Water is the major constituent of the body. Total body water ranges from 60% to 80% of body weight. A newborn infant has close to 80% of body weight as water, whereas a child over the age of 12 months has approximately 60%. Since adipose tissue has very little water and approximately 80% of muscle tissue is water, a muscular child will have proportionately more water when compared to an obese child.
Total body water (TBW) is divided into 2 major compartments: intracellular fluid (ICF), which is 40% of body weight, and extracellular fluid (ECF), which is 20% of body weight. ECF is further divided into interstitial (16% of body weight) and plasma (4% of body weight) volumes. At birth, ECF is approximately 1.5 times that of ICF. However, this changes rapidly to become almost equal to ICF by day 10 of life. ICF gradually increases in proportion to become twice as much as ECF by age 3 years, and this proportion (two-thirds of TBW is ICF and one-third of TBW is ECF) is maintained thereafter. The compositional difference between interstitial fluid and plasma is mainly related to plasma proteins. Plasma volume is maintained by the oncotic pressure exerted by plasma proteins (primarily albumin). Thus, plasma measurement of electrolytes and acid-base is representative of the values for ECF.
ICF and ECF volumes maintain their proportions because water moves from one compartment to another through water channels (aquaporins) in the cell membrane to achieve osmotic equilibrium. When particles are restricted to 1 compartment, they will hold water with them so that water will not cross to the other compartment. Sodium (Na) and its coupled anions, mainly chloride (Cl) and bicarbonate (HCO3), are the particles restricted to ECF and thus control the ECF volume. Potassium (K) and its coupled anions, macromolecules such as organic phosphates, are restricted to ICF and control its volume. These macromolecules are essential for cellular function, and therefore, their concentration is nearly constant. Hence, change in the ratio of particle to water comes about largely as a result of change in the content of water in the ICF. Thus, water has to move into or out of ICF, from or into ECF, to make a change in the volume of the ICF. This requires a change in the concentration of Na in the ECF (plasma) because only then there will be a change in the osmotic equilibrium between ICF and ECF to allow for water movement to achieve a new osmotic equilibrium. Hence, almost always ICF volume increases (swollen cell) when plasma Na concentration decreases (hyponatremia), and ICF volume decreases (shrunken cell) when plasma Na concentration increases (hypernatremia) (Fig. 462-1). There are some notable exceptions to this relationship: following rhabdomyolysis, small osmotically active particles are produced within the ICF increasing the osmotic forces inside the cell so that water moves from ECF to ICF. Here, there is hypernatremia, and yet the cell is swollen. Another exception relates to urea in renal failure patients. Since urea crosses most cell membranes rapidly, its concentration is the same in both ECF and ICF compartments. Thus, urea does not function as an effective osmole under normal circumstances. An exception to this may occur in the brain following hemodialysis in children with renal failure. During hemodialysis, there can be a rapid decline in plasma urea. However, urea transport across the blood-brain barrier does not occur as rapidly as the decline in plasma urea. Accordingly, brain urea concentrations may remain elevated, causing water to move into the brain, increasing cell volume and intracranial pressure with resultant coma or death.
Cell volume changes with alterations in extracellular fluid tonicity. The circle represents the cell membrane. Normal cell volume is depicted by the light red–shaded area. On the left side of the figure, the cell is placed in a hypotonic environment, which causes water to enter the cell, and the cell swells, as shown by the dark red–shaded area. On the right side of the figure, the cell is placed in a hypertonic environment with resultant water flux out of the cell, and the cell shrinks as shown by the dark red–shaded area.
An important fact to understand is that although Na is restricted mainly to the ECF, in practical terms, it acts like as if it is also in the ICF due to its effect on water movement between the 2 compartments. Thus, when considering Na or water disorder, both have to be taken into account and analyzed to determine the mechanism(s) causing the disturbance as well as to plan therapy.
Maintenance of cell volume is extremely important for normal cell function and structural integrity. All cells maintain their volume by cell volume regulation, which causes them to lose or gain particles to adapt to the change in ECF osmolality in order to counteract cell swelling or shrinking. Acute exposure to a hypotonic ECF causes cells to swell within a few minutes. Shortly thereafter, cell volume begins to decrease toward normal due to the loss of intracellular solutes, particularly potassium. Conversely, exposure to a hypertonic ECF causes cells to decrease in size and then recover via a net movement of solutes (mostly Na and Cl) into the cell. However, a change in these inorganic ions can disrupt intracellular enzyme systems. Some cells, such as brain cells, utilize an additional mechanism generating idiogenic osmoles from cellular metabolism to control cell volume. These osmoles, including taurine, glycine, glutamine, sorbitol, and inositol, do not disrupt intracellular protein functions. Increases in idiogenic osmoles have been detected in brain cells as early as 4 hours after an acute hypertonic challenge and persist for several hours. Loss or reduced uptake of these idiogenic osmoles has been noted with hyponatremia. By 48 hours, most adaptations have occurred and the cell has returned to near-normal volume. In essence, although adaptation begins rapidly, it takes several hours to maximize, and despite cell volume regulation, the cell does not return to its original size (Fig. 462-2).
Cell volume regulation. The circle represents the cell membrane. Normal cell volume is depicted by the light red–shaded area. When the cell is placed in a hypotonic environment (A), it goes through the stages as depicted by the arrows. Initially, water enters the cell and it swells, as shown by the dark red–shaded area. Both electrolytes and osmolytes are rapidly lost from the cell and its volume is returned to near normal level, but still slightly swollen. When the cell is placed in a hypertonic environment (B), it goes through the stages as depicted by the arrows. Initially, water leaves the cell and it shrinks, as shown by the dark red–shaded area. Both electrolytes and osmolytes are rapidly gained in the cell, and its volume is returned to near normal level, but still slightly shrunken.
Compartment volumes are regulated by integrated mechanisms. These include hypothalamic regulators that control fluid and electrolyte intake and renal water excretion (osmoreceptors, arginine vasopressin [AVP]), the renin–angiotensin–adrenal system, and the atrium (atrial natriuretic peptide [ANP]) in response to changes in sodium concentration and extracellular and plasma volumes. In brief, even a small increase in plasma osmolality (1%) is detected by the “osmoreceptor” in the anterior hypothalamus and induces thirst and water intake. It also increases secretion of AVP, which increases renal water reabsorption. The converse occurs with decreased plasma osmolality.
The intact kidney responds to diminished renal perfusion such as occurs with decreased plasma (ECF) volume in a predictable and consistent manner. Initially, the glomerular filtration rate is maintained by afferent arteriolar vasodilatation and constriction of the efferent arteriole. Because renal plasma flow is diminished, protein concentration and osmotic pressure are increased in the postglomerular capillaries. This results in enhanced peritubular capillary reabsorption and a nearly maximal reabsorption of sodium in the proximal tubule. Volume contraction also stimulates aldosterone secretion in response to elevated angiotensin II and renin secretion, resulting in maximal sodium reabsorption in the distal tubule and early collecting duct. Together, these forces result in a nearly maximal retention of the filtered load of sodium. Volume depletion also increases the water permeability of the collecting ducts via actions of AVP; enhanced water reabsorption in this final segment of the nephron results in an increase in urinary osmolality. Thus, when renal perfusion or plasma volume is diminished, the physiologic sequence of events that affect both salt and water reabsorption combines to increase intravascular volume.
ANP is produced in the atrium. Secretion is increased by atrial stretch and a variety of other factors induced by hypervolemia. ANP acts on the kidney to increase sodium and water excretion. It also inhibits renin and aldosterone secretion, thus increasing sodium excretion.
The kidneys play a very important role in maintaining plasma osmolality and ECF volume. As can be appreciated from many clinical situations, if the hormonal milieu is different than what is expected from normal physiology, if there is impaired renal function, if the child has an impaired thirst mechanism, or if there no access to water, Na and water disturbance can result very easily and sometimes unexpectedly. Thus, a high index of suspicion for such disturbances should be entertained by physicians caring for children, especially if the child is to be treated with parenteral fluid therapy.
How does a physician know how much water and electrolytes, particularly sodium and potassium, to give to a child? To answer this question, the concept of maintenance fluid and electrolyte therapy will be reviewed.
MAINTENANCE FLUID AND ELECTROLYTE THERAPY
The fundamental fluid requirements for maintenance therapy were derived from the metabolic rate and energy expenditures of normal children. As defined by Holliday and Segar, “maintenance” therapy is a fluid prescription (water, sodium, and potassium) designed to replace the expected water and electrolyte losses in order to maintain euvolemia and electrolyte balance in normal children. They observed that the rate of caloric expenditure was relatively linear for infants and children in 3 weight categories: 100 calories/kg for 1 to 10 kg, 50 calories/kg for 11 to 20 kg, and 20 calories/kg for 21 to 80 kg. After 2 endogenous sources of water, water of oxidation and preformed water, have been taken into account, fluid requirements are 100 mL of exogenous water for every 100 kcal of energy expended. Thus, a single sliding scale can be used to calculate an estimate of both caloric expenditure and total maintenance fluid volume. For example, in a child who weighs 14 kg, an estimate of caloric expenditure or maintenance fluid requirement would be 1000 mL for the first 10 kg plus 50 mL/kg for the next 4 kg or 200 mL, for a total of 1200 mL/d, or similarly, a caloric expenditure of about 1200 kcal/d. By the same approach, the hourly rate of fluid therapy would be 40 mL/h (for the first 10 kg) plus 2 mL/h for next 4 kg, or 48 mL/h. For patients weighing more than 80 kg, the relationship between body weight and water distribution diverges significantly, so that this sliding scale calculation is likely to overestimate fluid requirements.
Maintenance fluid provides for losses from only evaporative (insensible) sources and urinary losses under normal physiologic conditions.
Maintenance fluid = insensible water loss + urine loss
It does not take into account fluid lost from the gastrointestinal tract (diarrhea) or from the circulating volume into interstitial volume (third spacing, ascites).
Solute-free water that evaporates from the skin and lungs is termed insensible water loss (IWL) because losses from these sites are not readily appreciated. Water is evaporated from the lungs for thermal regulation and to humidify inspired air and from the skin to regulate core body temperature by means of convection and conduction. Skin losses are not ordinary sweat. In the usual environment, and under normal physiologic conditions, IWL amounts to about one-third of the calculated maintenance fluid (40% in infants and 25% in adolescents; Table 462-1). Increased IWL should be anticipated when children are hyperthermic or tachypneic, are placed under a radiant warmer, or are exposed to a dry or hot environment. Hyperthermia greater than 38°C increases IWL by 12.5% per 1°C. In contrast, evaporative fluid losses are reduced when children receive humidified air or become hypothermic. The proportion of IWL is about two-thirds via skin and one-third via lungs.
TABLE 462-1MAINTENANCE WATER AND ELECTROLYTES ||Download (.pdf) TABLE 462-1MAINTENANCE WATER AND ELECTROLYTES
|Measure ||Average Value |
|Insensible water (mL/100 kcal) ||40 |
|Metabolic watera (mL/100 kcal) ||−15 |
|Urinary water (mL/100 kcal) ||75 |
|TOTAL ||100 |
|NaCl (mmol/100 kcal) ||3 |
|K (mmol/100 kcal) ||2 |
Maintenance fluid volume is predicated on the ability of the kidney to excrete isosthenuric urine (specific gravity 1.010; urine osmolarity 280–310 mOsm/L). Urinary losses are assumed to account for 60% to 75% of maintenance volume under normal physiologic conditions (Table 462-1). For younger children, urine output is anticipated at approximately 2 to 3 mL/kg/h.
The estimation of the volume of urine excreted per day is not simple. Two important factors have to be considered. One is that the kidney should be able to concentrate or dilute. If the concentrating ability is impaired (eg, diabetes insipidus, prematurity, sickle cell disease), more water will be excreted, and if the concentrating ability is enhanced (increased AVP release for any reason), less water will be excreted. The second factor is the osmolar load the kidney has to excrete. If the osmolar load is increased (administration of total parenteral nutrition or glucosuria in diabetes mellitus), there will be an increase in the urinary water excretion, and if the load is reduced (starvation or low-Na diet), the urinary water excretion will be reduced.
Thus, an appreciation for changes in urinary output and IWL from what would be estimated under normal conditions (maintenance fluid) is imperative in designing appropriate fluid therapy for an ill child. If not, the child can receive too little or too much water, both of which can lead to deleterious outcomes, including death, as a result of neurologic injury.
Composition of Maintenance Fluid
This must account for electrolytes (Na, K, and Cl) as well as energy needs. Based on empiric studies, 3 mmol of sodium and chloride and 2 mmol of potassium are required for each 100 kcal expended, which is extrapolated to the requirement for each 100 mL of fluid lost (Table 462-1). These electrolytes will maintain homeostasis and allow for new cell growth in normal children. Therefore, the parenteral fluid solution recommended almost 60 years ago for maintenance fluid therapy contained 30 mmol/L of sodium and chloride, 20 mmol/L of potassium, and 50 g/L of dextrose (sufficient to avoid ketosis and endogenous protein catabolism). It is important to understand that this “maintenance fluid prescription” was proposed by Holliday and Seger for children who were unable to ingest fluids but were otherwise healthy, euvolemic, had normal renal handling of sodium, water, and potassium, and did not have ongoing abnormal fluid and electrolyte losses.
Over time, this “maintenance fluid prescription” has somehow evolved to be given to children with more losses than normal (dehydration) and for ECF volume expansion. Since most children requiring some form of parenteral fluid therapy also have several reasons for high levels of AVP (eg, nausea, vomiting, pain, medications, anesthesia, circulating blood volume contraction, meningitis) with ensuing water retention, hyponatremia may be a dangerous complication when fluid that is more hypotonic than plasma is administered intravenously. This has led to controversy regarding the optimal electrolyte composition that should be recommended for initial maintenance fluid. Some authors recommend that isotonic saline be administered to all children to avoid hyponatremia, but others are concerned that isotonic saline can produce hypernatremia. A recent systematic review and meta-analysis by Foster and colleagues found that administration of hypotonic maintenance fluid increased the risk of hyponatremia when compared to isotonic fluid. As Friedman in his editorial comment on this paper points out, much has been learned about the pathophysiology of production, release, and action of AVP since the original proposal on “maintenance fluid therapy.” He advocates that intravenous fluid therapy be recognized as a prescription much like antibiotics or chemotherapy and should be individualized with frequent assessment and appropriate monitoring.
Therefore, starting therapy with a solution that has an Na concentration that matches the plasma appears to be less dangerous until it is known what the electrolyte composition and volume of the urine are and the estimated IWL is in a child. In a child with normal serum Na concentration (SNa), this would be isotonic saline. If there is no contraindication (eg, anuria), K should be added (20–30 mmol/L) based on the serum K concentration (SK). This should be followed by serial measurements of the concentrations of urinary Na (UNa) and K (UK), osmolality, and urinary flow rate, as well as SNa and SK. In addition to measurement of urinary flow rate, other losses (diarrhea, vomiting) should also be measured. These will provide information as to whether the child has normal AVP activity (normal urine output with specific gravity of 1.010 or urine osmolality of 280–310 mOsm/L) and the quantity of water, Na, and K lost. Once these are available, therapy can be refined to match the losses of both water and electrolytes so that the SNa and SK will remain within the normal range (135–145 mEq/L and 3.5–4, respectively).
Total parenteral nutrition (TPN) does not always have to be given in the form of isotonic saline. Generally, a solution with 30 mmol/L of Na and 20 mmol/L of K given in a volume to match all output (urine and IWL) as per the metabolic demand calculation will maintain the normal water, Na, and K levels as long as the kidney is able to either retain or excrete the water, Na, and K to maintain homeostasis and there is no other unusual losses (eg, cystic fibrosis, diarrhea, vomiting, polyuria). The composition of commonly administered intravenous fluid is presented in Table 462-2.
TABLE 462-2COMPOSITION OF COMMONLY ADMINISTERED INTRAVENOUS SOLUTIONS ||Download (.pdf) TABLE 462-2COMPOSITION OF COMMONLY ADMINISTERED INTRAVENOUS SOLUTIONS
| ||Na, mmol/L ||K, mmol/L ||Cl, mmol/L ||Lactate, mmol/L ||Osmolality, mOsm/L |
|Isotonic or normal saline ||154 ||0 ||154 ||0 ||308 |
|Half-normal or 0.45% saline ||77 ||0 ||77 ||0 ||154 |
|0.2% normal saline ||30 ||0 ||30 ||0 ||60 |
|D5W or 5% dextrose water ||0 ||0 ||0 ||0 ||278 |
|D5W and half-normal saline ||77 ||0 ||77 ||0 ||432 |
|Ringer’s lactate ||130 ||4 ||109 ||28 ||271 |
|Plasma-Lyte 148 ||140 ||5 ||98 ||0a ||294 |
Once these calculations have been made and an appropriate fluid administration is begun, ongoing evaluation of the adequacy and composition of the fluid is essential. This evaluation has to be based on changes in body weight, SNa and SK, urine volume (flow rate) and specific gravity or osmolality, UNa and UK, and the overall status of the patient. Thus, all children receiving parenteral fluid therapy must have accurate measurement and charting of fluid balance (input and output) and should ideally be weighed daily. Because fluid therapy with D5W (5% dextrose in water) provides for only 20% of the caloric expenditure, patients can be anticipated to lose 0.5% to 1% body weight per day. If the volume of fluid being administered is less than full maintenance volume (all losses), and the concentration of glucose in that fluid is not increased, the loss of body weight will be even greater. If adequate fluids and electrolytes to meet the ongoing losses (primarily urine and IWL) are provided, increased weight combined with a fall in SNa suggests excessive water administration. This should prompt the physician to check the input and output of water to determine if the output has decreased but has not been recognized. This is extremely important since the etiology of oliguria may be iatrogenic or otherwise (unrecognized AVP release) and requires evaluation. In contrast, a very rapid loss of weight, combined with increased SNa and/or a persistent tachycardia, would suggest inadequate water replacement, and an assessment of factors that might be increasing water loss must be undertaken. One may therefore use “maintenance fluid calculation” as a starting point for rate of administration of water when parenteral fluid therapy is being designed, but the child has to be continually assessed since fluid and electrolyte requirement is an ongoing and dynamic process that requires careful attention to all of the factors mentioned above.
Infants and young children are particularly susceptible to dehydration mainly because of relatively larger body surface area from which fluid evaporates and the inability to access water or Na and partly because of the limited ability of the kidney to maximally concentrate the urine. Three essential assessments must be performed in the evaluation of a child with dehydration: (1) estimate the degree or severity of the dehydration, (2) determine the type of deficit, and (3) develop and implement a plan to repair the deficit.
Estimation of the Degree and Severity of Dehydration
This is based primarily on the patient’s history, clinical condition, and laboratory data at the time of initial presentation. Although this estimation is mostly based on clinical observations, each of these may be altered due to reasons other than dehydration and therefore requires great care in the interpretation (Table 462-3). For example, capillary refill is highly susceptible to environmental conditions such as ambient temperature, and heart rate may be increased due to pain or fever. A change in body weight, if available, is very helpful. However, no one factor can predict the degree or severity of dehydration.
Mild dehydration (1–5%): The findings are largely historically based, ie, a history of 12 to 24 hours of vomiting/diarrhea, with no change in urine output other than the possibility of a slight decrease in frequency indicating the production of a concentrated urine and minimal findings on physical examination.
Moderate dehydration (6–10%): In addition to the history of fluid loss, there is also a history of reduced urine output (oliguria) and increased thirst (if thirst was intact) plus the physical findings, which include tenting of skin, sunken eyes and fontanel, slight lethargy, and dry lips and mouth.
Severe dehydration (11–15%): The patient will usually develop findings of cardiovascular instability (mottling of skin, tachycardia, hypotension) and neurologic involvement (extreme irritability, coma).
TABLE 462-3SEVERITY OF DEHYDRATION BASED ON HISTORY AND EXAMINATION ||Download (.pdf) TABLE 462-3SEVERITY OF DEHYDRATION BASED ON HISTORY AND EXAMINATION
|Symptoms and Signs ||Mild ||Moderate ||Severe |
|Pulse ||Full, normal rate ||Rapid ||Rapid, weak |
|Systolic blood pressure ||Normal ||Normal to ↓ ||Shock |
|Urine output ||↓ ||↓↓ ||Anuria |
|Buccal mucosa ||Slightly dry ||Dry ||Parched |
|Anterior fontanelle ||Normal ||Sunken ||Markedly sunken |
|Eyes ||Normal ||Sunken ||Markedly sunken |
|Skin turgor ||Normal ||↓ ||Tenting |
|Skin ||Normal ||Cool ||Cool, mottling, acrocyanosis |
This initial assessment is almost always subjective unless a change in body weight has been documented. Although the evaluation of a specific patient by several skilled observers may produce widely varying estimates of the degree of dehydration, this assessment is essential and provides one of the key elements for developing a plan for deficit fluid therapy. Laboratory values such as plasma concentrations of urea and albumin, in addition to hematocrit, are helpful if a previous measurement is known. Dehydration over a protracted period may be more severe than initially clinically evident.
The word dehydration is a misnomer since it appears to refer to water loss only and does not provide information on which compartment of the TBW has suffered a loss. It also fails to inform the physician whether there is only water loss or Na loss or both and in what proportion. This is very important since the tonicity or effective osmolality of the ECF determines the size of the ICF. The brain is in a tight compartment (skull) and does not tolerate changes in volume well, particularly if the changes are acute; such changes are associated with significant morbidity and mortality, including coma and death. Thus, defining the type of dehydration is extremely important not only for the purposes of investigating the underlying disorder but also for designing appropriate therapy. The type of dehydration is defined by the tonicity of the patient’s serum. On this basis, states of dehydration are commonly referred to as isotonic (SNa 135–145), hypotonic (SNa < 135), and hypertonic (SNa > 145).
There is an isotonic fluid loss from the ECF, ie, there is both Na and water loss equal to the tonicity of plasma. For example, if a child had lost 1 L of isotonic fluid from the ECF (10% dehydration in a child with a body weight of 10 kg when healthy), it means that the deficit is 1 L of water and 135 to 145 mmol of Na. Most children present with this type of dehydration. The ECF volume is contracted, but ICF volume remains the same. Thus, the danger to the child is only from ECF volume loss and not because of change in cell volume, which can result in cerebral edema or hemorrhage and has a much higher associated morbidity and mortality. Therapy is designed to replace the losses from the ECF (ie, give 1 L of isotonic saline) and, once ECF volume is restored, replace ongoing losses for water and electrolytes: IWL, urine, and any other losses.
There is a hypertonic loss of fluid from the ECF, ie, there is a loss of both sodium and water, but the proportion of sodium loss is greater. This may occur if a child with ongoing fluid and electrolyte losses has access to hypotonic fluids (water and juice) or is given hypotonic intravenous fluid such that there is gain of water without a corresponding gain in sodium. For example, if a child has 10 L of ECF volume and has an SNa of 130 mmol/L with the estimated ECF volume loss of 1 L and a normal SNa of 140 mmol/L, the Na loss is 230 mmol [(140 mmol/L × 10 L) – (130 mmol/L × 9 L)], whereas the water loss is only 1 L. Because the pathophysiologic adaptation to ECF volume loss causes AVP release, among other things, water excretion is limited. Thus, the patient who has fluid loss (water and electrolytes) and takes in an appreciable quantity of water with minimal electrolyte content will develop hypotonicity and hyponatremia. This should not be confused with a hyponatremic state without “dehydration,” which is seen in a patient with congestive heart failure (CHF); here, there is no “dehydration,” but rather an increase in both Na and water content of the ECF; however, the proportional increase in water is more than Na. In CHF, this is as a result of decreased effective circulating volume with an increase in AVP, angiotensin II, aldosterone, and thirst. The result is that TBW is increased with expansion of interstitial fluid volume and ensuing edema.
There is a hypotonic loss of fluid from ECF, ie, although there is a loss of both Na and water, water loss is greater than Na loss. This may be due to impaired thirst, inability to obtain water, and/or problems with water absorption in the gut or reabsorption in the kidney. In an infant, incorrect mixing of the formula may lead to less water intake compared to output, resulting in negative water balance. On the other hand, there may be only Na gain and no water loss at all, such as in true salt poisoning, which is rare. In true salt poisoning, the patient does not have ECF volume depletion, but rather expansion. In hypertonic dehydration, the water loss in excess of electrolyte loss may be from the gastrointestinal tract (osmotic diarrhea), skin (heat stroke), or kidneys (diabetes insipidus).
All types of dehydration require an assessment of the effective circulating volume. The goals of initial therapy are to prevent or treat shock and improve perfusion to the brain, kidney, and gastrointestinal tract by expanding the intravascular volume. The rate and route of fluid administration depend on the severity of dehydration and whether the gut is able to absorb the administered fluid. All mild and most moderate dehydration can be treated with small, frequent administrations of oral rehydration solution (Table 462-4) as long as the gut is able to absorb it. Some moderate and all severe dehydration require parenteral therapy, at least initially. This is usually given as isotonic saline at volumes of 10 to 30 mL/kg, although some may require up to 60 to 100 mL/kg. Ringer’s lactate is another solution that can be used (see Table 462-2). However, it has K and lactate (metabolized by the liver to bicarbonate) and, therefore, should not be administered to a child with oliguria/anuria or vomiting with resultant metabolic alkalosis or to children with significant impairment of liver function. Fluid should be administered rapidly to expand the vascular volume first and then the total ECF volume. Studies have shown a fall in high levels of AVP to near normal values with aggressive fluid therapy and expansion of ECF volume in children with severe burn shock or acute diarrheal illness. This should be followed by oral or parenteral fluid that matches the tonicity of the patient’s plasma. The volume, composition, and rate of ongoing therapy after ECF volume has been expanded should match all of the output (IWL, urine, gut, or any other losses) so that euvolemia and plasma tonicity are maintained at normal levels. There are several fluid regimens published with the view to helping the physicians treating a child with dehydration. Although most have merit, it is dangerous to follow any particular regimen without a clear understanding of the basic principle, which is to replace what is lost in a 1-to-1 ratio to maintain homeostasis. Clinically it may be difficult to determine whether ECF volume has been restored. A reduction in heart rate and establishment of normal urinary flow rate (which in a normal young child is approximately 3 mL/kg/h) can be utilized as markers. Frequent measurements of weight, urine output, and serum electrolytes, with appropriate adjustment in administered fluids, are crucial to guide management. In isotonic dehydration, replacement of the deficit can be rapid. In contrast, deficit therapy should be slow in both hypotonic and hypertonic dehydration to avoid serious neurologic consequences. As discussed previously, brain cells accommodate to hypotonicity and hypertonicity with change in intracellular idiogenic osmoles that attempt to maintain cellular size and function. Rapid correction of ECF tonicity results in cellular swelling or shrinking, with resultant cerebral edema, and elevation in intracranial pressure or osmotic demyelination syndrome (ODS).
TABLE 462-4COMPOSITION OF COMMONLY USED ORAL REHYDRATION SOLUTIONS (ORS) ||Download (.pdf) TABLE 462-4COMPOSITION OF COMMONLY USED ORAL REHYDRATION SOLUTIONS (ORS)
|Type ||Na, mmol/L ||K, mmol/L ||Cl, mmol/L ||Citrate or HCO3, mEq/L ||Glucose, g/L (mmol/L) |
|Standard WHO ORS ||90 ||20 ||80 ||30 ||2 (110) |
|Reduced osmolarity WHO ORS ||75 ||20 ||65 ||30 ||13.5 (75) |
|Pedialyte ||45 ||20 ||35 ||30 ||2.5 (140) |
|Gastrolyte ||50 ||20 ||52 ||18 ||2 (110) |
Accurate calculation of K deficit is impossible because K is predominantly an intracellular ion. In addition, depending on factors including hormonal milieu and the metabolic status of the child, the administered K may not enter the cell. If renal function is impaired, the administered K will not be excreted and hyperkalemia can ensue, particularly if K is given too rapidly. Thus, for all types of dehydration, K should be administered only after the patient has voided and then administered in concentrations that generally do not exceed 40 mmol/L or a rate of infusion of 0.5 mEq/kg/h unless there is significant hypokalemia.
Hyponatremia arises from a net loss in sodium or a net gain in water. Since Na and its accompanying anions account for almost all the osmotic activity of the plasma (Posm), hyponatremia is generally associated with hypo-osmolality.
where 2 is for the osmotic contribution by the anion accompanying Na and 18 and 2.8 are to convert glucose and blood urea nitrogen (BUN), respectively, from mg/dL to mmol/L. Urea and glucose do not contribute to effective osmolality under normal conditions because they cross the cell membrane. However, in states of low or no insulin (diabetes mellitus), glucose acts as an effective osmole and causes water to shift from ICF to ECF, resulting in a fall in SNa (translocational hyponatremia). When mannitol and glycine are administered, they remain in ECF and cause a similar shift of water, resulting in hyponatremia. In both these instances, there is increased effective osmolality, but SNa is low without a true loss of total body Na or a true gain in TBW. However, in diabetic ketoacidosis due to prolonged glucosuria, the total body Na is reduced. Aside from these situations, SNa is a ratio between total body Na and TBW as depicted below.
Thus, a loss in Na or a gain in water can produce hyponatremia. Either way, in order to develop and maintain hyponatremia, there has to be a renal restriction to the excretion of water. This is due to either increased AVP release and/or activity or a significant reduction in glomerular filtration rate. In addition, a source of electrolyte-free water is required. This may come from water or hypotonic fluid intake (ingestion or intravenous administration) or hypertonic fluid loss (thiazide diuretics). Water and juice are the most common forms of electrolyte-free water ingestion in children.
Symptoms of hyponatremia result from cell swelling causing cellular dysfunction, especially of the brain cells. These can range from nonspecific symptoms such as anorexia, nausea, irritability, headache, and muscle cramps to more alarming central nervous system (CNS) manifestations such as disorientation, agitation, and seizures. Most importantly, hyponatremia can result in death due to cerebral edema and herniation of the brain. Thus, a high index of suspicion is required to associate these symptoms with hyponatremia. The symptoms and signs depend on whether the patient has acute (defined as ≤ 48 hours in duration) or chronic hyponatremia and the magnitude of the hyponatremia. Most patients with acute hyponatremia or those with chronic hyponatremia and a further acute decline in SNa will result in some symptoms and signs.
There is increasing evidence that chronic hyponatremia is associated with osteoporosis, fracture, gait instability, cognitive impairment, and attention deficit. Hence, even mild chronic hyponatremia requires diagnostic workup and therapy.
Assessment of Hyponatremia
The most important assessment is that of ECF volume. If it is low, the primary problem is that of Na loss. If the kidney is functioning normally, it should retain Na. Thus, if the UNa is < 10 mmol/L, the source of Na loss is extrarenal (Table 462-5) except in the case of prior vomiting or diuretic use. If the UNa and UK are high, the disorder is one of a Na-wasting nephropathy (Bartter syndrome), diuretic use, or vomiting. When ECF volume is normal or high, the primary problem is that of water gain (Table 462-6). Most often this is due to increased release and/or activity of AVP whether due to a low effective circulating volume or to other nonosmotic and nonbarometric stimuli. The causes of syndrome of inappropriate antidiuretic hormone (SIADH) are many, including neoplasia, CNS and pulmonary disorders, psychosis, pain, nausea, vomiting, and drugs. An activating mutation leading to increased sensitivity of V2 receptors in the kidney also results in water retention and chronic hyponatremia and is often included in the etiology of SIADH, although some refer to it as nephrogenic syndrome of inappropriate antidiuresis because AVP levels are very low or undetectable. Water gain may also be due to low water delivery to the distal nephron (renal failure) resulting in decreased water excretion.
TABLE 462-5ETIOLOGY OF HYPONATREMIA IN LOW EXTRACELLULAR FLUID VOLUME STATE ||Download (.pdf) TABLE 462-5ETIOLOGY OF HYPONATREMIA IN LOW EXTRACELLULAR FLUID VOLUME STATE
|UNa < 10 mmol/L ||UNa > 20 mmol/L |
1. Nonrenal loss
2. Previous renal loss
Renal loss (current)
TABLE 462-6ETIOLOGY OF HYPONATREMIA IN NORMAL OR HIGH EXTRACELLULAR FLUID VOLUME STATE ||Download (.pdf) TABLE 462-6ETIOLOGY OF HYPONATREMIA IN NORMAL OR HIGH EXTRACELLULAR FLUID VOLUME STATE
|Normal Effective Circulating Volume ||Low Effective Circulating Volume |
Hyponatremia has to be corrected because it is associated with significant morbidity and mortality. The approach and urgency may vary depending on presenting symptoms and chronicity. Acute hyponatremia is defined as hyponatremia that is less than 48 hours in duration, and chronic hyponatremia is defined as when the duration is longer than 48 hours. This is primarily based on studies on cell volume regulation, particularly the brain cells. All patients without a previously documented serum sodium (most patients presenting to the emergency department) should be considered to have chronic hyponatremia. Rapid correction of serum sodium (> 8 mmol/L/24 h) in patients with chronic hyponatremia can result in significant neurologic consequences, including osmotic demyelination syndrome (ODS), and should therefore be avoided. ODS can result in minor neurologic and cognitive dysfunction that may be transient or in permanent major sequelae such as paraplegia or death. Patients who are at particularly high risk of developing ODS are those who have liver failure, hypokalemia, and malnutrition.
When acute hyponatremia is diagnosed, it may be in the setting of an already hospitalized patient in whom preceding 24- to 48-hour laboratory values for SNa are available. Postoperative hyponatremia is one such entity. Others include recreational drug use such as “Ecstasy” and exercise-associated hyponatremia. Many of these patients are asymptomatic, and their SNa is low due to relative excess of TBW compared to total body Na. If they are asymptomatic, no specific therapy may be required other than restriction of electrolyte-free water intake because the hyponatremia will usually correct itself once the stimulus for AVP is no longer present. The rate of spontaneous correction does not appear to result in adverse effects such as ODS. Therapy to reduce AVP stimulation such as an antiemetic for nausea may also aid in the management. If patients are symptomatic, rapid correction of the hyponatremia is imperative to prevent cerebral edema and associated morbidity. The magnitude of correction should be 4 to 6 mmol/L. There is no evidence that increases beyond this range add further benefit, and in a patient who may have acute on chronic hyponatremia, a higher rate of correction may be harmful.
If the patient has acute symptoms such as seizures that are determined to be due to the hyponatremia, it is safe to rapidly raise the SNa by 4 to 5 mmol/L regardless of whether the patient has acute or chronic hyponatremia. This can be achieved by administering 3% NaCl, which has approximately 513 mmol of Na in each liter. For example, in a 10-kg child who has 60% TBW, the Na required to raise the SNa by 5 mmol/L is 30 mmol (10 × 0.6 × 5) and the volume of 3% NaCl required is 58 mL [(30) × (1000 ÷ 513)]. For ease of calculation, one can assume that 1 mL of 3% NaCl provides 0.5 mmol NaCl. Thus, in this example, the child will require 60 mL (instead of 58 mL; not a clinically significant difference) of 3% NaCl to provide the 30 mmol of Na needed.
Once the acute symptoms subside, the goal of therapy is to raise the SNa by no more than 3 mmol/L during the rest of the 24 hours so that the total correction for the 24 hours is only 8 mmol/L. In order to minimize adverse events, the rate of correction should be about 0.3 mmol/L/h (equivalent to a total correction of 8 mmol/L/24 h). Depending on the etiology of the hyponatremia (primary water gain or Na loss), either water should be restricted or Na should be given. In order to accomplish this, all water and electrolyte losses (IWL, urine, and others) must be accounted for. Therefore, all losses have to be measured accurately and frequently and replaced or restricted accordingly.
In the above example of a 10-kg child, if Na loss is felt to be the etiology, then a total of 18 mmol of Na (10 × 0.6 × 3 mmol/L) has to be given over 24 hours in addition to what was already given and what is being replaced for losses. If water gain is felt to be the cause, and the SNa is 120 mmol/L after the initial 3% NaCl administration, then all electrolyte losses have to be replaced 1:1, and a negative water balance (150 mL) should be aimed for as shown by the calculation below.
where 6 kg is the TBW (60% of 10 kg).
Another way to calculate the negative water balance is as follows: Assume that the fall in SNa is due to water gain and that the number of total osmoles in the body has not changed. Since Posm is primarily due to Na, the following equations will solve for the water gain.
Thus, this gain of water needs to be lost. Since the IWL in this child with 10-kg body weight is close to 300 mL/d and IWL has very little electrolytes, the child can be given only 150 mL of the IWL as replacement to allow for a negative water balance of 150 mL (∼6 mL/h).
In cases of hyponatremia without significant neurologic symptoms, 3% NaCl should not be administered even if the serum sodium is very low. In an asymptomatic patient, the hyponatremia is probably a chronic, long-standing condition. Gradual correction of hyponatremia is safer. An important fact to bear in mind is that when the ECF volume is low and has been restored, the stimulus for AVP release can be abolished, resulting in water diuresis. If not anticipated, such a water diuresis can raise the SNa much more rapidly than envisioned. Administration of desmopressin (DDAVP) can be considered in patients with a rapid correction of serum sodium due to such water diuresis to curtail the water loss and slow the rate of correction of SNa. In the case of overcorrection, animal studies and some case reports in adult patients have shown that the development of ODS can be prevented by re-lowering SNa with the administration of DDAVP and/or electrolyte-free water.
Hypernatremia is very similar to hyponatremia in concept and principle. It is due to either a gain in total body sodium or a loss in TBW. In general, water loss from the ECF is accompanied by water loss from the ICF and loss of body weight. Exceptions to this relationship are found in cases of prolonged seizure or rhabdomyolysis where cellular swelling occurs because of the generation of osmotically active particles in the cells causing water to shift from ECF to ICF, without a change in TBW or body weight. Most often, hypernatremia is due to the loss of water. Rarely, true sodium retention occurs as a result of administration of hypertonic NaCl, sodium bicarbonate (NaHCO3), or sodium-rich oral formula, and this is usually accompanied by an increase in body weight. In the analysis of the etiology of hypernatremia, thirst, access to water, gastrointestinal absorption of water, and renal reabsorption of water are all major considerations and should be evaluated (Table 462-7). Since only a 2% increase in plasma tonicity (a rise in serum sodium from 140 to 143 mmol/L) results in intense thirst, either a defect in thirst mechanisms or a lack of access to water must also be present during the genesis of hypernatremia. Hypernatremia should also stimulate the release of AVP so that the urine will be of minimum quantity and maximum osmolality.
TABLE 462-7ETIOLOGY OF HYPERNATREMIA ||Download (.pdf) TABLE 462-7ETIOLOGY OF HYPERNATREMIA
|Water Loss > Sodium Loss ||Lack of Water Intake ||Sodium Gain > Water Gain |
High ambient temperature
Lack of antidiuretic hormone activity and/or impaired concentrating ability (nephrogenic or central diabetes insipidus, reflux nephropathy, sickle cell nephropathy, drugs)
Osmotic diuresis (glucose, urea, mannitol)
|Hypothalamic Dysfunction |
Loss of “osmoreceptor” function with absence of thirst
Lack of Access to Water
Unable to verbalize need for water (infant, young child, central nervous system disorder, intubation)
Unable to obtain water, as in paralysis, intentional water restriction (child abuse), inability to swallow water (dysphagia)
Sodium bicarbonate administration
Accidental Salt Ingestion
Error in preparation of infant formula
Sea water ingestion
The symptoms and signs of hypernatremia are similar to those of hyponatremia with the involvement of the CNS and muscles. These include irritability, lethargy, weakness, seizures, coma, and death. Shift of water out of brain cells with ensuing decrease in brain volume causes rupture of cerebral veins resulting in intracerebral and subarachnoid hemorrhages. Symptoms develop according to the rapidity (rate of rise) with which hypernatremia develops. The minimum level at which symptoms appear to develop in acute hypernatremia is when the SNa is 158 mmol/L. However, with chronic hypernatremia, symptoms may not develop until a much higher SNa level, likely due to adaptation with cell volume regulation.
Assessment of Hypernatremia
Just as in hyponatremia, assessment of ECF volume provides substantial information. If ECF volume is expanded, Na gain is likely, and if reduced, a negative balance for water is more likely. Body weight is very helpful in these situations. Next, assess the urine for volume and osmolality. If the urine volume is high and the osmolality is not maximal, there is renal water loss. If urine volume is low and the osmolality is maximal, there is nonrenal water loss. In either situation, access to water or thirst must also be affected. Causes of hypernatremia as listed in Table 462-7.
Therapy for Hypernatremia
Just as in hyponatremia, cell volume regulation begins as soon as hypernatremia develops and brings the brain cell volume back to near normal by 48 hours. Thus, therapy has to be slow in chronic hypernatremia or else brain cells will swell, resulting in cerebral edema. Therefore, correction of SNa should not exceed 0.3 mmol/L/h (8 mmol/L/24 h), except in the case of a patient with symptoms such as seizures, in which case, the aim should be to correct SNa by 3 to 4 mmol/L initially and then to follow the guidelines. This can be achieved by calculating the water deficit and replacing it. To calculate the water deficit, assume that the rise in SNa is due to water loss and that the number of total osmoles in the body have not changed. Since Posm is primarily due to Na, the following equations will solve for the water deficit.
If the current body weight is 10 kg, the current TBW is 60% of current weight, and the current TBW is 6 L (10 × 0.6). If the current SNa is 170 mmol/L and the New SNa (target) is 140 mmol/L:
The serum sodium correction of 30 mmol/L (170 – 140) should not exceed the recommended rate of 8 mmol/L/24 h. Hence, the calculated water should be administered over about 90 hours [(30 ÷ 8) × 24]. Therefore, the rate of water deficit administration should begin at about 14 mL/h (1290 mL ÷ 90 hours). The water deficit can be administered orally or intravenously (dextrose water). Once water deficit therapy is started, the patient should be monitored closely to determine if all losses are being replaced appropriately so that the SNa does not fall too rapidly. It should be remembered that all ongoing losses (IWL, urine, and others) have to be replaced in a 1:1 ratio for both water and electrolytes in addition to water deficit therapy. When K is added to the fluid, it increases the tonicity; for example, if a solution has 40 mmol/L Na and 30 mmol/L K, the tonicity is more close to half-isotonic saline.
Potassium is the most abundant intracellular cation (98% of total body content) and plays a fundamental role in cellular homeostasis. Total body potassium is maintained at about 50 mmol/kg body weight with only a small quantity (< 1 mmol/kg) in the ECF. When there is a significant rise or fall in SK, there is a predisposition to cardiac arrhythmias. Therefore, SK is tightly maintained against a concentration gradient that favors movement of K from ICF to ECF. This is mainly due to a complex system that involves the actions of Na+-K+-ATPase and hormones including insulin and catecholamines (particularly β-adrenergics) (Fig. 462-3). Thus, potassium intake (oral or parenteral) must be distributed immediately to avoid a dangerous increase in the serum potassium; the ICF acts as the sink. However, the extra potassium eventually has to be excreted. The kidneys increase or decrease the rate of excretion of potassium to maintain potassium balance. The intestinal mucosa is also capable of excreting some potassium in chronic hyperkalemia.
Cellular mechanisms for K shift into cells. The big circle represents the cell membrane. The oval structures indicate (1) Na+-K+-ATPase and (2) NHE (sodium hydrogen exchanger). Na+-K+-ATPase pumps 3 Na+ out of cells and 2 K+ into cells and maintains the negative voltage inside cells. This is activated by β-adrenergics. Under the influence of insulin, NHE transports Na+ into cells and H+ out of cells.
K Physiology and the Kidney
The excretion of K by the kidney involves 2 mechanisms: 1 is the active secretion of K primarily by the distal tubule and the collecting duct, and the other is urine flow rate.
K excretion = urine K concentration (UK) × urine volume
Factors that influence UK are aldosterone activity, the presence or absence of non–re-absorbable anions such as bicarbonate, sulfate, or phosphate in the lumen, and sodium delivery. Urine volume is influenced by diuretic agents, urea, sodium, and water delivery.
Assessment of K Disorders
Evaluation of patients with disorders of potassium requires an evaluation of (1) potassium intake, (2) shift of potassium into or out of cells, and (3) potassium excretion, which is mainly by the kidneys, although the gastrointestinal tract and skin may also contribute, especially in chronic hyperkalemia. It must be remembered that the serum potassium constitutes a very small portion of total body potassium and that alterations in the serum potassium may not be a reflection of overall total body potassium balance.
Hypokalemia is defined as SK less than 3.5 mmol/L. Most clinical problems related to hypokalemia are due to K wasting by the kidneys. As K intake decreases, renal K excretion decreases markedly to maintain homeostasis. Thus, although a reduced K intake can compound an already existing hypokalemia, it is almost never the sole cause of hypokalemia. Causes of hypokalemia include (1) shifts in potassium from the ECF to ICF, (2) excessive nonrenal potassium excretion, and (3) increased renal potassium excretion (Table 462-8).
TABLE 462-8CAUSES OF HYPOKALEMIA ||Download (.pdf) TABLE 462-8CAUSES OF HYPOKALEMIA
|Increased Shifts in Potassium from Extracellular to Intracellular Fluid Compartments |
|During insulin therapy for diabetic ketoacidosis |
|β2-Adrenoreceptor agonists (salbutamol, epinephrine, norepinephrine) |
|Barium ingestion |
|Hypokalemic periodic paralysis |
|Digitalis therapy |
|Excessive Nonrenal Potassium Excretion |
|Gastrointestinal fistula |
|Excessive sweating |
|Excessive Potassium Secretion by the Distal Nephron |
High plasma aldosterone and renin levels with metabolic acidosis
High plasma aldosterone and renin levels with metabolic alkalosis
Low plasma aldosterone and renin levels (usually with high blood pressure)
Acute hypokalemia arises in diverse contexts (see Table 462-8). Increased K shift from ECF to ICF is generally the cause of acute hypokalemia. Serum potassium decreases following treatment of diabetic ketoacidosis due to the movement of potassium into the cell (see Fig. 462-3). This is compounded by increased excretion of urinary potassium with glucose-induced diuresis, once effective circulating volume is restored. Patients with diabetic ketoacidosis are particularly susceptible to hypokalemia because they already have low total body K due to glucose-induced diuresis as part of their disease process and may present with apparent hyperkalemia due to metabolic acidosis and lack of insulin. Potassium shifts into cells when plasma pH is high (alkalosis) and SK can decline by 0.2 mmol/L for each 0.1-unit increase in pH. Catecholamines, particularly β2-adrenergics, increase K shift into cells by activating Na+-K+-ATPase. Catecholamines also increase glycogenolysis and indirectly increase insulin levels. Thus, any patient receiving therapy with such agents (salbutamol, epinephrine, and norepinephrine) and those with head injury where there is a markedly increased sympathetic nervous system activity can develop significant hypokalemia. Other conditions such as barium ingestion, hypokalemic periodic paralysis, hypothermia, and therapy with digitalis also shift K into cells.
With long-standing diarrhea or gastrointestinal fistula, significant hypokalemia can develop with metabolic acidosis due to potassium bicarbonate loss. Vomiting or nasogastric suctioning result in metabolic alkalosis and volume contraction, which increase renal potassium excretion.
Although the K concentration in sweat ranges from 5 to 10 mmol/L, profuse sweating seen with strenuous exercise or cystic fibrosis can result in hypokalemia due to 3 reasons: (1) K loss through skin, (2) K loss by kidneys due to activation of aldosterone from ECF volume contraction, and (3) shift of K into cells due to catecholamine release from ECF volume contraction.
Excessive renal potassium excretion results from either excessive urinary flow rate or increased urine potassium concentration. High urinary flow rate occurs with excretion of a large amount of osmoles (eg, urea, glucose, mannitol), diuretics, and salt-wasting nephropathies (renal tubular acidosis, Bartter syndrome, and Gitelman syndrome). In these situations, urinary potassium concentration may be low because of the large volume of water giving the false impression that renal loss of potassium is not significant. An inappropriate renal response to hypokalemia is assessed by the transtubular potassium gradient (TTKG), which is calculated as TTKG = (urine potassium × serum osmolality)/(serum potassium × urine osmolality). The TTKG is a valid indicator of the renal response when urine osmolality is greater than 300 and urine sodium is greater than 25. It is expected to be less than 2 in hypokalemia. The most common hypokalemic states are associated with high plasma aldosterone levels. Thus, most tubulopathies result in hypokalemia due to both a high urine flow rate and a high urine potassium secretion.
Amphotericin B and ifosfamide are tubular toxins and are felt to cause a potassium leak, which can result in significant hypokalemia. Vomiting requires special mention because it causes hypokalemia by several mechanisms. Hydrochloric acid is lost from the stomach with vomiting, and the ECF gains HCO3. This results in metabolic alkalosis and increases the filtered load of HCO3. The ensuing loss of HCO3 with sodium causes ECF volume contraction and consequently activation of the renin–angiotensin–aldosterone system. Increases in both the distal delivery of HCO3 and aldosterone activity stimulate potassium secretion. In addition, when potassium ion (K+) shifts out of cell, for electrical neutrality, hydrogen ion (H+) moves into cell from ECF, causing further rise in ECF HCO3 (ie, worsening of metabolic alkalosis).
Assessment of Hypokalemia
Generally, the history and clinical examination are adequate to determine the cause of hypokalemia (vomiting, diarrhea, diuretics, or polyuria). Hypertension suggests high aldosterone or mineralocorticoid-like activity that is not due to ECF volume contraction. To confirm the suspected diagnosis, the following tests may be used: (1) urine K excretion/24-hour urine for K, spot UK, and TTKG, (2) plasma levels of aldosterone and renin, and (3) metabolic acid-base status. In both K shift and nonrenal loss, urine K excretion will be low.
Hypokalemia can induce life-threatening cardiac arrhythmias, particularly when digitalis is given at the same time, and respiratory compromise mainly due to muscle weakness. It also causes paralytic ileus, rhabdomyolysis, and renal dysfunction, especially urinary concentrating defect when the hypokalemia is chronic. Thus, a patient with hypokalemia may require emergency therapy with K supplement by the intravenous route. The usual dose for potassium replacement is 0.5 to 1 mEq/kg intravenously, not to exceed 30 to 40 mEq/dose. The infusion rate should not exceed 0.3 to 0.5 mEq/kg/h except in life-threatening cases of hypokalemia. Administration of potassium should be accompanied by electrocardiograph monitoring to detect the potential onset of arrhythmias observed with hyperkalemia. The type of potassium salt to use will depend on the metabolic acid-base status: potassium bicarbonate (KHCO3) or potassium citrate when there is metabolic acidosis and potassium chloride (KCl) with metabolic alkalosis. Whenever possible, oral repletion is preferable; in severe hypokalemia that may be associated with ileus, this is not possible. Oral supplementation is based on body weight, ranging from 2 to 4 mEq/kg/d in divided doses to avoid gastric irritation. Since the total body potassium deficit cannot be calculated and is usually large with chronic hypokalemia, correction to the normal range often requires repeated dosing over many days.
Hyperkalemia is defined as SK more than 5.5 mmol/L. Electrocardiographic (ECG) changes are generally not seen until SK is 6 mmol/L; however, there is no correlation between the 2. Reduced renal K excretion is almost always present in chronic hyperkalemia. Pseudohyperkalemia due to hemolysis is very common in young children and infants with difficult venipuncture. Lysis of white blood cells and platelets during clotting if there is significant leukocytosis and thrombocytosis can also raise SK spuriously.
Just as in hypokalemia, excess K intake by itself does not produce hyperkalemia unless there is compromised renal K excretion due to its great capacity to excrete K. In addition, colonic K excretion in chronic hyperkalemia is not insignificant. Autoimmune hemolytic anemia can rarely cause hyperkalemia, especially if renal function is impaired. When a small child is given a large red blood cell transfusion, the K load may be too high to be excreted immediately and hyperkalemia can ensue. Shift of K out of cells tends to result in acute hyperkalemia. Shift of K may occur with metabolic acidosis (SK increases by about 0.2 mmol/L for every 0.1-unit decline in pH), lack of action of insulin, or tissue catabolism (tumor lysis syndrome). More often, there is more than 1 contributing factor. Depolarization with the muscle relaxant succinylcholine can raise SK, especially in children with neuromuscular disorders or burns. Hyperkalemic periodic paralysis is another rare cause. It is particularly important to remember that although a β-adrenergic antagonist does not cause hyperkalemia on its own, under certain situations (lack of insulin and/or metabolic acidosis, especially if renal function is compromised), it can compound the severity of hyperkalemia.
Renal K excretion is reduced due to either a low K secretion by the distal nephron or a low-volume delivery to the distal nephron. Often there is a combination of the 2 causes. Thus, it is not surprising that children with predominantly distal nephron damage (reflux nephropathy, obstructive nephropathy, sickle cell disease) are especially susceptible to hyperkalemia. Gordon syndrome (familial hypertension with hyperkalemia) is a rare genetic disorder caused by defective modulators of salt transporters, including the thiazide-sensitive NaCl cotransporter. Common causes of hyperkalemia, including acute and chronic renal failure, volume depletion, and impaired aldosterone activity, are listed in Table 462-9.
TABLE 462-9CAUSES OF HYPERKALEMIA ||Download (.pdf) TABLE 462-9CAUSES OF HYPERKALEMIA
|Increased Potassium Intake |
|Potassium Shift from Intracellular to Extracellular Fluid Compartment |
Tumor lysis syndrome
Metabolic acidosis (especially diabetic ketoacidosis)
Hyperkalemic periodic paralysis
|Reduced Renal Potassium Excretion |
Acute renal failure
Chronic renal failure
Gordon syndrome (familial hypertension and hyperkalemia)
Calcineurin inhibitors (tacrolimus and cyclosporine)
|Impaired Aldosterone Activity |
Low plasma aldosterone level
Congenital adrenal hyperplasia
Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker
Nonsteroidal anti-inflammatory agent (usually transient)
High plasma aldosterone level
Aldosterone receptor blocker (spironolactone)
Aldosterone insensitivity due to distal nephron damage such as reflux nephropathy, obstructive uropathy, sickle cell disease
Assessment of Hyperkalemia
A thorough history and clinical examination are crucial in identifying the etiology of hyperkalemia. Increase amplitude and peaking of the T wave, as well as other changes in the ECG, are helpful in confirming the diagnosis (Fig. 462-4). In the setting of hyperkalemia, a low TTKG (< 10) indicates impairment of renal potassium excretion. The underlying etiology should be explored by pursuing the potential causes listed in Table 462-9.
Electrocardiograph showing changes associated with hyperkalemia.
Hyperkalemia is better tolerated when chronic. The severity of ECG changes correlates with the rate of rise in serum potassium and not with the absolute serum potassium value. When ECG changes occur (see Fig. 462-4), urgent therapy should be provided to stabilize the myocardium (calcium gluconate) and to rapidly shift potassium into cells (insulin and glucose, NaHCO3, and/or β-agonist). This should be followed by specific therapy to remove potassium from the body, which includes colonic exchange of potassium for sodium or calcium with a cation-exchange resin, increasing renal potassium excretion with improved renal perfusion, and/or diuretic administration (loop or thiazide diuretic) and dialysis. All sources of potassium administration should be removed (intravenous and dietary). Details of treatment are outlined in Table 462-10. In less severe cases, removal of exogenous K administration (dietary and intravenous) alone and/or administration of cation-exchange resins and diuretics may suffice. Dietary K load from milk may be reduced by treating the formula with a cation-exchange resin prior to feeding the child and choosing a formula with lower K content.
TABLE 462-10TREATMENT OF HYPERKALEMIA ||Download (.pdf) TABLE 462-10TREATMENT OF HYPERKALEMIA
|Therapy ||Dose ||Peak Effect ||Complications |
|Step 1. Antagonism of membrane actions of potassium |
|Calcium gluconate ||1 mL/kg of 10% solution IV over 2–3 min ||∼5 min ||Hypercalcemia, bradycardia |
|Step 2. Shift potassium into cells |
|Insulin and glucose ||Glucose 0.5 g/kg; insulin 0.1 U/kg IV over 30 min ||∼2 h, lasts several hours ||Hypoglycemia, hypophosphatemia |
|Sodium bicarbonate ||0.5 mmol/kg IV over 10–15 min ||∼30–60 min, lasts several hours ||Hypernatremia, hypocalcemia, metabolic alkalosis |
|β-Adrenoceptor agonist ||5–20 mg nebulizer ||∼90 min ||Tachycardia, hypertension |
|Step 3. Remove potassium from the body |
|Cation-exchange resin ||1–2 g/kg PO or PR in sorbitol ||∼2–4 h ||Hypernatremia, constipation, colonic necrosis |
|Diuretics || || || |
|Hemodialysis or peritoneal dialysis || || || |
The hydrogen ion (H+) concentration in the body is very tightly controlled by complex buffer systems to avoid adverse effects on cellular function. Normal plasma H+ concentration is 40 ± 2 nmol/L, a very tiny quantity when compared to most other ions, which are in millimolar concentrations. This equates to a pH of 7.35 to 7.45. When the pH is outside of this range, there is an acid-base disorder. Each day, an adult produces approximately 1 mmol/kg H+ during normal metabolism. The most important and abundant buffer system that manages this acid load is the bicarbonate (HCO3) buffer system, which is very efficient because the lungs eliminate the carbon dioxide (CO2) that is produced when HCO3 buffers the added H+ produced from metabolism. Thus, as more H+ is added, more CO2 is produced, via the reaction:
continuously moving toward the right as more H+ is added. The kidneys reabsorb all of the filtered HCO3− load and also regenerate the HCO3− that buffered the added H+ so that the total body HCO3− content remains the same. The relationship of this buffer system is described by the Henderson-Hasselbalch equation. In clinical practice, the concentration of H2CO3 is expressed as the partial pressure of CO2 (PCO2).
When the plasma pH is less than 7.35, there is acidemia and the process that caused this is acidosis. If there is retention of CO2, there is respiratory acidosis, and if there is loss of HCO3−, there is metabolic acidosis.
When the plasma pH is more than 7.45, there is alkalemia, and the process that caused this is alkalosis. If the PCO2 is low, there is respiratory alkalosis, and if there is retention of HCO3−, there is metabolic alkalosis.
Usually there exists a primary process that causes the disturbance in pH and a secondary process that attempts to compensate for the altered pH. However, compensation is almost never complete; consequently, there is always acidemia or alkalemia. For example, in a primary metabolic acidosis, the lungs compensate by eliminating more CO2, which results in respiratory alkalosis. Table 462-11 provides the approximate expected changes in both HCO3− and CO2 when there is an acid-base disturbance. A convenient rule of thumb to consider is “drop the 7 and decimal point,” where if lungs are responding appropriately to metabolic acidosis, PCO2 should be the same as the 2 numbers following the decimal point when the 7 is dropped from pH. For example, if pH is 7.30, PCO2 should be close to 30 mm Hg.
TABLE 462-11APPROXIMATE COMPENSATORY CHANGES IN HCO3− AND PCO2 WITH ACID-BASE DISORDERS ||Download (.pdf) TABLE 462-11APPROXIMATE COMPENSATORY CHANGES IN HCO3− AND PCO2 WITH ACID-BASE DISORDERS
|Type of Disorder ||pH ||HCO3− ||PCO2 |
|Metabolic acidosis ||↓ ||↓ ||Fall by 1–1.5 × the fall in HCO3− |
|Metabolic alkalosis ||↑ ||↑ ||Rise by 0.25–1 × the rise in HCO3− |
|Acute respiratory acidosis ||↓ ||Rise by 0.1 × the rise in PCO2 ||↑ |
|Chronic respiratory acidosis ||↓ ||Rise by 0.35 × the rise in PCO2 ||↑ |
|Acute respiratory alkalosis ||↑ ||Fall by 0.1–0.3 × the fall in PCO2 ||↓ |
|Chronic respiratory alkalosis ||↑ ||Fall by 0.2–0.5 × the fall in PCO2 ||↓ |
In metabolic acidosis, the low plasma pH is due to a lowering of plasma HCO3– concentration. This may be due to addition of acid or loss of HCO3−. The patient will have increased rate and depth of breathing due to respiratory compensation, which begins within minutes of lowering of pH. Anion gap, which is due to unmeasured anions (primarily albumin), is helpful in determining the etiology.
Anion gap = measured cations – measured anions = SNa+ − (SCl– + SHCO3–)
An increase in anion gap indicates added acid (anion) such as ketones (in ketoacidosis) and lactate with poor perfusion. Other causes of an increased anion gap metabolic acidosis are toxic ingestion of, for example, methanol (formic acid), ethylene glycol (glyoxylic acid), ethanol (ketoacids), and salicylate (acetylsalicylic acid); retention of acids with renal failure; and lactate or organic acid production from inborn errors of metabolism.
Non–anion gap metabolic acidosis is due to HCO3− loss and is accompanied by high serum chloride concentration, and is thus also called hyperchloremic metabolic acidosis. The most common cause is gastrointestinal loss of Na and K bicarbonate. If a large quantity of chloride is infused intravenously, there is dilutional as well as real lowering of HCO3– concentration. Renal tubular acidosis is another cause where there is loss of HCO3− and/or impaired ammonium excretion.
Diagnosis and Therapy of Metabolic Acidosis:
The diagnosis and therapy depend on history and clinical examination. Most children with diarrheal illness will not require bicarbonate therapy unless they have significant ongoing losses or there is renal impairment, because kidney is able to generate large quantities (4–5 times normal) of HCO3− with increased ammonium excretion to compensate for the loss. Once ECF volume is expanded and perfusion to the kidney improves, HCO3− will be generated in such patients. Most poisonings give rise to an osmolar gap (measured osmolality – calculated osmolality) in the plasma and require specific therapy.
In metabolic alkalosis, the increase in plasma pH is due to a rise in plasma HCO3−concentration when metabolic alkalosis is the primary disorder. Respiratory compensation is in the form of retention of CO2. Metabolic alkalosis requires 2 mechanisms: first, the generation of metabolic alkalosis, and second, the maintenance of metabolic alkalosis. Generation of metabolic alkalosis can be due to a loss of H+ from either the gastrointestinal tract or kidney or due to a shift of H+ into cells. It can also be due to retention of administered alkali such as in the case of excessive administration of NaHCO3. With any cause of ECF volume contraction and sweat loss in children with cystic fibrosis (chloride loss), contraction alkalosis may develop and requires therapy with NaCl. The most common gastrointestinal causes include vomiting and nasogastric suctioning or drainage from a gastrostomy tube. Congenital chloride-losing diarrhea is a rare cause of metabolic alkalosis. Renal causes include diuretic therapy (loop and thiazide), mineralocorticoid excess, hypercalcemia, and post–chronic hypercapnia. The latter requires therapy with chloride to expand ECF volume due to prior loss of chloride in exchange for bicarbonate (renal compensation for respiratory acidosis) without which the metabolic alkalosis will not resolve. A shift of H+ into cells occurs during refeeding in malnutrition and with prolonged hypokalemia.
Once metabolic alkalosis develops, it has to be maintained. The kidney can facilitate “maintenance” of high concentration of plasma HCO3− due to either decreased glomerular filtration rate, increased tubular reabsorption of HCO3−, or a combination of both. Hypokalemia from any cause, hyperaldosteronism (endogenous and exogenous), and decreased effective circulating volume result in the latter. Diagnosis and therapy depend on the etiology.
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