866 71 Fluid and Electrolyte Issues in Pediatric Critical Illness IDRIS V R EVANS AND EMILY L JOYCE • Hypotonic maintenance intravenous (IV) fluids are associated with mild to moderate hyponatremia in[.]
71 Fluid and Electrolyte Issues in Pediatric Critical Illness IDRIS V.R EVANS AND EMILY L JOYCE • Traditional fluid and electrolyte management during critical illness is being refined by science, clinical experience, and expert opinion Particular attention is drawn to intravenous fluid (IVF) composition, appropriate uses and choices of colloids, extracellular fluid (ECF) volume targets from resuscitation to maintenance, and approaches to removal of excessive ECF volume using diuresis, continuous renal replacement therapy (CRRT), and intermittent hemodialysis (IHD) Fluid and electrolyte management often begins at resuscitation, but important choices are also made at anesthesia induction and at initial postoperative maintenance Resuscitation with normal saline is physiologically effective and cost-effective in almost all circumstances.1 However, the chloride content imposes an acid load.2 Further, there are substantial data suggesting potential harm from fluids containing supraphysiological concentrations of chloride3–5 and improved outcomes for certain patients with balanced crystalloid solutions.6,7 Increasing evidence highlights the importance of evaluating resuscitative fluid composition for specific patient populations Similarly, intraoperative fluids influence acidbase and electrolyte status, particularly of vulnerable patients.8 The Na1 content of IVF for postoperative or critical care maintenance may be important for certain patients Clearly, 0.180 and 0.225 mM saline are associated with a higher incidence of mild hyponatremia,9,10 although controlled trials not show this effect for 0.460 mM saline.11,12 Severe hyponatremia has been infrequently associated with pulmonary or central nervous system (CNS) illness in pediatrics, with the exception of children with traumatic brain injury (TBI) Among patients with those and 866 • Hypotonic maintenance intravenous (IV) fluids are associated with mild to moderate hyponatremia in postoperative patients Anesthesia, stress, and inflammatory mediators may contribute Electrolyte monitoring in patients at risk is essential for detection and management of severe hyponatremia This critical effect of the syndrome of inappropriate antidiuretic hormone may occur even in patients on isotonic IV fluids Growing evidence suggests that the choice of normal saline crystalloids, balanced solution crystalloids, or colloids for • • PEARLS resuscitation and maintenance therapy should be influenced by the underlying pathology Albumin infusions have been generally safe but may introduce increased mortality risk in patients with traumatic brain injury Those given albumin had increased intracranial pressure, which may contribute to the apparent risk Avoiding and correcting excessive fluid volume overload after initial resuscitation and hemodynamic stabilization will decrease morbidity and mortality among critically ill patients other illnesses, the evolving study of the influence of inflammatory mediators directly on the hypothalamus and indirectly on vasopressin secretion may further clarify which patients are at most risk of clinically significant hyponatremia.13,14 Evidence for and against the use of colloids in specific groups of critically ill patients is accumulating Intriguing but less than definitive studies suggest benefit in sepsis and septic shock15–18 and possible harm in patients with TBI, perhaps associated with increased intracranial pressure.19 Albumin does appear useful in stabilizing patients with severe hepatic failure and in prevention of hepatorenal syndrome.20–22 Evidence for albumin use with or without diuresis among those with acute respiratory distress syndrome (ARDS) suggests improved oxygenation but minimal effect on outcomes.23 In general, in patients with relatively intact vascular endothelium, 10 to 15 mL/kg of 4% or 5% albumin may be used for intravascular volume expansion with slower leakage into the ECF space compared with crystalloids Albumin concentrate at 25% may be useful in temporarily redistributing ECF volume from the extravascular to the intravascular space to facilitate organ perfusion and spontaneous or drug-assisted diuresis with minimal additional infused fluid volume In summary, consideration of albumin use in selected patients remains appropriate.24,25 Currently, there are no formulations of hydroxyethyl starch that can be recommended for use in critically ill patients.26,27 Adult and pediatric studies have generated strong evidence for deleterious effects of fluid volume overload, particularly in patients with sepsis or ARDS.28,29 Patients with less fluid gain early in their illness have more ventilator-free days, shorter CHAPTER 71 Fluid and Electrolyte Issues in Pediatric Critical Illness intensive care unit (ICU) stays, less acute kidney injury (AKI), and decreased in-hospital mortality compared with those with greater than 5% to 15% early positive fluid balance.30–35 The observed associations of increasing fluid balance on morbidity and mortality has led to proposals of a phased approach to fluid management, including aggressive resuscitation using appropriate fluids guided by careful clinical measurement and evaluation, prompt reduction of resuscitation fluid rates when hemodynamically tolerated, gradual correction of volume excesses using fluid restriction, colloid dosing to adjust fluid space distribution, continuous infusion diuresis, and, finally, CRRT or IHD when needed.36–39 Medications are a potentially overlooked and modifiable source of excess fluid volume in patients with fluid volume overload.40,41 As ICU patients progress from stabilization to maintenance, ECF volume overload may spontaneously resolve, or it may warrant active intervention Loop diuretics not prevent or ameliorate AKI42 but may be useful in mobilizing excess ECF volume.43 Studies of this intervention are variable as to dosages, patient diagnoses, and renal conditions Carefully titrated continuous infusion of loop diuretics may be superior to bolus dosing.44–47 In ARDS, continuous infusion plus albumin have enhanced fluid mobilization.48–50 Accompanying losses of K1, Ca11, and Mg11 should be anticipated and replaced appropriately For patients unresponsive to diuresis, either CRRT or IHD can provide electrolyte management, and gradual ECF correction though the optimal timing of CRRT among different patient groups is under evaluation.51–56 Sodium Sodium distribution is 90% extracellular and, with its associated anions, largely determines the osmotic condition of the ECF Disturbance of ECF osmolality affects cell volume, with critical clinical significance in the CNS Therefore, neurologic symptoms dominate the clinical picture in both hyponatremia and hypernatremia In pediatric patients in the ICU, young age, underlying neurologic conditions, developmental delay, cerebral hypoperfusion, and medication effects may obscure subtle neurologic findings; judicious laboratory monitoring along with careful clinical assessment is essential Emerging evidence in both adult and pediatric patients suggests an association between disturbances in sodium balance and adverse outcomes, including mortality, ICU length of stay (LOS), use of both noninvasive and invasive mechanical ventilation, and long-term neurologic sequelae.57–63 It is unclear at this time whether these adverse effects are a direct consequence of the sodium imbalance, a reflection of a greater severity of illness, or related to other underlying pathologic processes Mild disturbances of sodium may serve as a warning of an ongoing process of greater significance More severe hyponatremia or hypernatremia may be life threatening.64 These disturbances may result from the disproportionate gain or loss of either sodium or water Pathologic sodium retention may occur in disorders such as congestive heart failure (CHF), cirrhosis, and nephrotic syndrome without causing a significant change in ECF concentration, but the concomitant expansion of the ECF volume may be damaging Hyponatremia Sudden, severe hyponatremia is life threatening Its management demands prompt, measured action with ongoing monitoring and 867 therapeutic adjustment The syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) are the most common causes of severe hyponatremia, although inappropriately dilute feeding or iatrogenic causes should also be considered Severe hyponatremia, which is variably defined as a serum sodium concentration of either less than 125 mEq/L or less than 120 mEq/L, is uncommon and is usually associated with known risk factors such as pulmonary or CNS disease or the use of certain drugs Mild hyponatremia is common among hospitalized pediatric patients and occurs predictably in postoperative patients Patients with renal, hepatic, or cardiac disease and those exposed to prolonged general anesthesia are particularly at risk Accurate identification of patients at risk will inform decisions on frequency of laboratory monitoring and will allow an early evaluation of and response to evolving hyponatremia Pathophysiology and Etiology Hyponatremia may occur in the presence of decreased, increased, or normal amounts of total body sodium (eBox 71.1) Decreased Total Body Sodium Loss of total body sodium results in hyponatremia if total body water is retained in relative excess of the sodium loss Hypovolemic stimulation of antidiuretic hormone (ADH) release may overwhelm osmotic ADH control, maintaining water retention despite hyponatremia and hypoosmolality A decrease of as little as 5% in circulating volume may be sufficient to trigger this response.65 Sodium deficit and volume loss may occur through extrarenal or renal losses In children, extrarenal losses most often occur from vomiting and diarrhea In critically ill patients, large extrarenal losses may result from fluid sequestration that occurs with sepsis, peritonitis, pancreatitis, ileus, rhabdomyolysis, ventriculostomy drains, and burns Renal losses include diuretic use, osmotic diuresis, various salt-losing renal diseases, CSW, and adrenal insufficiency.66 Renal Sodium Losses Renal salt-wasting states are generally identified by a urinary sodium excretion in excess of 20 mEq/L and a fractional excretion (FENa) of more than 1% The use of thiazide and loop diuretics can exacerbate hyponatremia and hypovolemia and lead to a characteristic hypokalemic metabolic alkalosis (i.e., contraction alkalosis) In normally functioning kidneys, concentrated urine is produced by the equilibration of fluid in the collecting tubules with the hyperosmotic medullary interstitium, which, in turn, is generated by sodium chloride (NaCl) reabsorption without water in the ascending limb of the loop of Henle Thiazides act in the cortical distal tubule and not impair the ability of ADH to increase water reabsorption in the collecting tubules and collecting duct,67 resulting in thiazide-associated hyponatremia Osmotic sodium and water losses occur in a child with uncontrolled hyperglycemia with glucosuria, with mannitol use, and during urea diuresis following relief of urinary tract obstruction Hyperglycemia and mannitol, in addition to inducing urinary sodium and water losses, produce osmotic water movement from the intracellular fluid (ICF) to the ECF, further lowering serum sodium Sodium levels drop about 1.5 mEq/L for every 100 mg/dL rise in blood glucose level Significant salt wasting may occur with several intrinsic renal diseases Adrenal insufficiency is identified by hyponatremia in association with hyperkalemia and decreased urinary potassium excretion 867.e1 • eBOX 71.1 Causes of Hyponatremia Decreased Total Body Sodium Extrarenal Vomiting/diarrhea Sequestration: sepsis, peritonitis, pancreatitis, rhabdomyolysis, ileus Cutaneous: burns, cystic fibrosis Ventriculostomy drainage Renal Cerebral salt wasting Diuretics Thiazides, loop diuretics (listed in order of severity of salt wasting) Osmotic diuretic agents: mannitol, glucose, urea Tubulointerstitial diseases Medullary cystic disease, obstructive uropathy, tubulointerstitial nephritis, chronic pyelonephritis, renal tubular acidosis, Kearns-Sayre syndrome Adrenal insufficiency Congenital adrenal hyperplasia, Addison disease Increased Total Body Sodium Congestive heart failure Cirrhosis Nephrotic syndrome Advanced chronic kidney disease Normal Total Body Sodium Syndrome of inappropriate antidiuretic hormone secretion Glucocorticoid deficiency Hypothyroidism Infantile water intoxication Abusive water intoxication 868 S E C T I O N V I I Pediatric Critical Care: Renal Cerebral Salt Wasting Cerebral salt wasting (CSW) is a clinical entity that continues to generate controversy First described by Peters and coworkers in 1950, it was superseded by the description of SIADH by Schwartz and coworkers in 1957 and then rediscovered in 1981 when Nelson and associates studied hyponatremia in a series of neurosurgical patients with isotopically measured low blood volumes.68 Despite lingering skepticism, its distinct clinical identity continues to be supported (Table 71.1).69–72 Patients typically have an acute neurologic injury with hemorrhage, trauma, infection, or a mass and may have undergone neurosurgical procedures, although CSW is not exclusively associated with intracranial abnormalities CSW differs from SIADH primarily related to intravascular volume depletion that may be difficult to clinically differentiate when hyponatremia is first detected CSW, which may be more appropriately labeled renal salt-wasting syndrome, is caused by inappropriate natriuresis that results in volume depletion whereas SIADH is caused by inappropriate water retention that results in (often subclinical) volume expansion (Table 71.2).73,74 With the natriuresis in CSW, large urine volumes contain very high sodium concentrations, leading to rapid depletion of both sodium and ECF volume An otherwise TABLE Cerebral-Renal Salt Wasting Syndrome 71.1 Trigger Most commonly, acute intracranial injury or illness (subarachnoid hemorrhage, trauma, etc.) though can be seen with non-CNS disease Onset Typically, a few days after the injury occurs Signs Falling serum Na1, high urine output, high urine Na1 Course Without treatment, proceeds to intravascular volume depletion, hypotension, and hypoperfusion Treatment Replace salt and water losses; may require 3% NaCl loop diuretics; fludrocortisone in refractory cases Resolution Days to weeks Differential diagnosis Syndrome of inappropriate antidiuretic hormone, adrenal insufficiency, osmotic diuresis CNS, Central nervous system TABLE Cerebral Salt Wasting (CSW) vs Syndrome of 71.2 Inappropriate Antidiuretic Hormone (SIADH) CSW SIADH Very high, often 100 mEq/L Can be lower if fluid and sodium are restricted Variable, but usually 20 mEq/L Urine output Inappropriately high, leading to volume depletion Variable; may be normal or decreased Response to saline challenge Improvement in volume deficit and serum Na1 No improvement in serum Na1 Response to fluid and salt restriction No improvement; volume deficit and hyponatremia may worsen Improvement in serum Na1 Urine Na unexplained intravascular volume contraction is central to the diagnosis and may cause a secondary boost in ADH release Left untreated, CSW results in intravascular volume depletion, hypotension, and hypoperfusion or hypovolemic shock as well as hyponatremia Untreated SIADH, in contrast, leads to progressive hyponatremia and the clinical consequences thereof with maintenance or mild expansion of fluid balance The pathophysiologic link between intracranial injury and renal salt wasting has yet to be elucidated, contributing in no small part to the controversy Both brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are attractive as potential mediators, but neither has a proven etiologic role.75,76 Decreased sympathetic input to the kidneys is another postulated mechanism.72 Distinguishing CSW from SIADH may be difficult in many complex clinical scenarios Urate clearance as a means to differentiate the two has shown promise in early studies,73 though the pathophysiology is not completely understood Hypouricemia and elevated urate clearance (FEUrate 12%) can be found in both SIADH and CSW, but only in CSW these abnormalities persist following correction of hyponatremia.73,74 In cases of severe or symptomatic hyponatremia, however, this may be temporarily unnecessary because the initial therapy is the same.68 Administration of enough concentrated sodium to result in a small increase in osmolality is appropriate, and support of intravascular volume is required A reasonable approach might begin with the administration of mL/kg of hypertonic (3%) NaCl followed by isotonic repletion of the remaining volume deficit Once this is achieved, sufficient sodium and fluid administration to account for daily maintenance requirements as well as ongoing losses is necessary Administration of fludrocortisone, a mineralocorticoid, has been reported to aid in CSW management in severe or prolonged cases that are refractory to initial therapy.72 In less severe cases, infusion of isotonic saline represents a reasonable first step in management; the observed response may help to differentiate between CSW and SIADH In CSW, saline administration addresses volume depletion and hyponatremia It is of limited or no benefit in patients with SIADH, who are more effectively managed with fluid restriction.70 The absolutely essential part of therapy is the frequent reassessment of sodium levels and volume status, with treatment adjustments as indicated Increased Total Body Sodium Hyponatremia with increased total body sodium occurs when the increase in total body water exceeds the sodium retention Four clinical situations are commonly seen: CHF, cirrhosis, nephrotic syndrome, and advanced renal failure In all four conditions, hyponatremia tends to be mild or moderate, asymptomatic, and nonprogressive or slowly progressive These patients typically present to the ICU primarily for care related to these underlying conditions rather than for symptoms related to hyponatremia Congestive Heart Failure Hyponatremia in heart failure is associated with a worse prognosis.77,78 Low cardiac output states are characterized by a decrease in effective circulating volume that is detected by vasoreceptors in the carotid sinus, aortic arch, and renal juxtaglomerular apparatus Activation of various neurohormonal modulators promotes vasoconstriction along with sodium and water retention Increased sympathetic activity and stimulation of the reninangiotensin-aldosterone system (RAAS) produce increased afferent and efferent arteriolar vascular resistance and decreased glomerular filtration rate (GFR) with a resultant decrease in urinary CHAPTER 71 Fluid and Electrolyte Issues in Pediatric Critical Illness sodium excretion Nonosmotic ADH release is stimulated, further impairing water excretion In addition, decreased aldosterone degradation, along with altered levels of other vasoactive and nonvasoactive substances, leads to a primary increase in tubular sodium reabsorption A deleterious positive feedback loop is created, in which the vasoconstrictive and fluid retentive effects of these neurohormonal systems promote further vasoconstriction and worsening renal perfusion.79 The complex interactions between renal and cardiovascular pathophysiology have been described as the cardiorenal syndromes, with five subtypes based on the primary organ affected and the acuity of the physiologic derangement.80 Cirrhosis Early in cirrhosis, increased intrahepatic pressure may initiate renal sodium retention even before ascites formation The development of portal hypertension leads to nitric oxide–mediated peripheral vasodilation and to the formation of arteriovenous fistulae The result is a decrease in effective circulating volume and activation of sodium-retaining mechanisms with higher levels of renin, aldosterone, ADH, and norepinephrine Hyponatremia arises in the setting of persistent renal sodium and water retention, which also leads to ascites and further complicates the kidneys’ ability to excrete water.81,82 Nephrotic Syndrome Hyponatremia is an occasional finding in patients with nephrotic syndrome However, it may be present in patients with apparently normal or decreased central volume The humoral factors involved in patients with decreased central volume appear to be similar to those with decompensated cirrhosis Renal Failure As a diseased kidney loses nephrons, the remaining nephrons exhibit a dramatically elevated fractional sodium excretion in an effort to maintain sodium balance Edema develops when larger quantities of sodium are ingested than cannot be excreted The ability to excrete water is also impaired, primarily because of the progressive decrease in GFR Hyponatremia occurs when water intake exceeds insensible losses plus the maximum volume that can be excreted Normal Total Body Sodium Hyponatremia without evidence of hypovolemia or edema in the pediatric population is usually associated with SIADH Renal concentrating and diluting ability ultimately depends on the presence or absence of ADH to modulate water permeability in the collecting duct Osmoreceptors for ADH reside in the anterior hypothalamus, responding to changes of as little as 1% in plasma osmolality The nonosmotic stimuli that induce release of ADH are associated with changes in autonomic neural tone due to physical pain or trauma, emotional stress, hypoxia, cardiac failure, nausea and vomiting, adrenal insufficiency, volume depletion, and exposure to general anesthesia (eBox 71.2) Nonosmotic stimuli, as the name implies, are active even in the face of normal plasma osmolality, and a decrease in plasma volume of as little as 5% is sufficient to trigger a strong ADH response.65 Vasopressin (ADH) synthesized in the hypothalamus is transported in neurosecretory granules to the axonal bulbs in the median eminence and posterior pituitary gland and is released by exocytosis in the presence of appropriate stimuli Increasing evidence indicates that inflammatory mediators facilitate release and contribute to the high incidence of hyponatremia in Rocky 869 Mountain spotted fever, Kawasaki, and other inflammatory illnesses.14 After release, ADH binds to V2 receptors in the basolateral membrane of the renal collecting duct, increasing cyclic adenosine 39,59-monophosphate formation and facilitating phosphorylation of aquaporin-2 Incorporation of aquaporin-2containing vesicles in the apical (luminal) membrane increases cell permeability to water and provides a pathway for water reabsorption.83 Clinically, SIADH is characterized by (1) hyponatremia, (2) euvolemia or mild hypervolemia, (3) hypoosmolality, (4) inappropriately elevated urine osmolality, and (5) elevated urine sodium concentration It has been associated with several categories of clinical disease, including CNS and pulmonary disorders, malignancies, and as an adverse effect of numerous drugs (see eBox 71.2).84 Underlying renal function is normal Under normal physiologic conditions, a decrease in serum sodium of to mEq/L below normal (with a serum osmolality of less than 270 mOsm) should maximally inhibit ADH secretion with a resultant urine osmolality of less than 100 mOsm It is frequently difficult to determine, however, whether urine osmolality and urine sodium are inappropriately elevated, particularly in critically ill patients receiving IV fluids Variable sodium and water administration rates, isotonic or hypertonic fluid boluses, fluctuations in hemodynamic status and urine output, and a history of diuretic use can all confound laboratory interpretation The key consideration is the relative relationship between the degree of hyponatremia and hypoosmolality and the robustness of the dilutional response in the urine Failure to maximally dilute urine in the face of hypoosmolality represents inappropriate ADH response so that a urine osmolality of 200 to 250 mOsm may reflect SIADH in hyponatremic patients The urinary sodium level is generally more than 30 mEq/L but may be much less in patients who are provided a low sodium intake.85 When the urinary sodium concentration is very high, it is the net balance between intake and output that differentiates between SIADH and CSW syndrome CSW is favored when the urinary sodium excretion grossly exceeds sodium intake Signs and Symptoms The severity of signs and symptoms depends on the rapidity of the development of hyponatremia Neurologic symptoms predominate as plasma hypoosmolality causes a shift in fluid from the ECF to the ICF compartment, leading to generalized cellular swelling The rigidity of the intracranial space leaves little room for cellular expansion, resulting in increasing intracranial pressure Brain cells prevent massive swelling in the early phases of hyponatremia by extrusion of electrolytes and other cellular osmolytes Acute decreases in sodium concentration are associated with lethargy, apathy, and disorientation, often accompanied by nausea, vomiting, and muscle cramps No predictable correlation exists between the degree of hyponatremia and its resultant symptoms, as severe hyponatremia that develops gradually may present with minimal symptoms Acute decreases in sodium to less than 120 mEq/L, however, generally produce severe symptoms, such as seizures or coma Other findings may include decreased deep tendon reflexes, pathologic reflexes, pseudobulbar palsy, and a Cheyne-Stokes respiratory pattern Cerebral edema and intracranial hypertension may be severe enough to result in herniation, permanent neurologic injury, and death.86 ... loop of Henle Thiazides act in the cortical distal tubule and not impair the ability of ADH to increase water reabsorption in the collecting tubules and collecting duct,67 resulting in thiazide-associated... noninvasive and invasive mechanical ventilation, and long-term neurologic sequelae.57–63 It is unclear at this time whether these adverse effects are a direct consequence of the sodium imbalance, a reflection... hypoosmolality A decrease of as little as 5% in circulating volume may be sufficient to trigger this response.65 Sodium deficit and volume loss may occur through extrarenal or renal losses In