869 e1 • eBOX 71 2 Nonosmotic Stimuli Associated With Syndrome of Inappropriate Antidiuretic Hormone CNS Disorders Infection Meningitis Encephalitis, including human immunodeficiency virus/acquired im[.]
869.e1 • eBOX 71.2 Nonosmotic Stimuli Associated With Syndrome of Inappropriate Antidiuretic Hormone CNS Disorders Drugs Infection Meningitis Encephalitis, including human immunodeficiency virus/acquired immunodeficiency syndrome encephalitis Brain abscess Rocky Mountain spotted fever Mass lesions Subarachnoid or subdural hemorrhage Cerebral thrombosis or hemorrhage Brain tumors Head trauma with cerebral edema Hydrocephalus Cavernous sinus thrombosis Guillain-Barré syndrome Multiple sclerosis Hypoxic encephalopathy, including neonatal hypoxic-ischemic encephalopathy Pituitary disease Acute psychosis Other Antidiuretic hormone analogs (vasopressin, desmopressin/1-deamino-8-Darginine vasopressin, oxytocin) Vincristine Salicylates Chlorpropamide Cyclophosphamide Carbamazepine Barbiturates Colchicine Haloperidol Fluphenazine Tricyclic antidepressants and selective serotonin reuptake inhibitors Clofibrate Indomethacin and nonsteroidal antiinflammatory drugs Interferon Ecstasy (3,4-methylenedioxy-methamphetamine) Pulmonary Disease Infection Bacterial and viral pneumonias Pulmonary abscess Tuberculosis Aspergillosis Asthma Respiratory failure with positive pressure ventilation Tumors Carcinomas of the lung, oropharynx, gastrointestinal tract (including the pancreas), and genitourinary tract Lymphoma, thymoma Ewing sarcoma, mesothelioma Miscellaneous High levels of inflammatory mediators Nausea/vomiting Pain or emotional stress General anesthesia Marathon running or endurance exercise Hereditary (gain-of-function mutations in the vasopressin V2 receptor) 870 S E C T I O N V I I Pediatric Critical Care: Renal Treatment Prevention Stimuli for ADH release are frequently present in both surgical and nonsurgical ICU patients, putting them at risk for hyponatremia Use of hypotonic intravenous (IV) maintenance fluids increases the risk for development of hyponatremia The appropriate administration of isotonic IV fluids in these patients will decrease the incidence of hyponatremia.9,10,87–92 For patients with severe SIADH or CSW, however, the use of isotonic fluids alone may not be adequate to prevent life-threatening disturbances in sodium and water balance Thoughtful monitoring of sodium levels is mandatory, along with avoidance of large volumes of hypotonic fluids Therapy The time course over which hyponatremia develops is a key determinant of the therapeutic approach Severe hyponatremia is associated with significant morbidity and mortality and requires urgent attention Even with milder hyponatremia, critically ill patients who have serum sodium corrected have improved rates of mortality and longer survival.93,94 As described previously, acute hyponatremia produces significant cerebral edema when initial compensation mechanisms are overwhelmed and more chronic adaptive mechanisms are not yet fully developed Hyponatremia that has been present less than hours can safely be corrected promptly When the evolution of hyponatremia is gradual, however, brain cells respond adaptively to prevent cerebral edema Thus, there are two essential questions in constructing a therapeutic plan: (1) did hyponatremia evolve rapidly or slowly, and (2) does the patient have CNS symptoms or imaging suggestive of cerebral edema? CNS cellular swelling and its symptoms are more likely with acute hyponatremia or with severe chronic hyponatremia.95,96 Symptomatic hyponatremia that develops suddenly—that is, in fewer than hours—can be rapidly reversed without incurring risk If asymptomatic hyponatremia has developed over many hours, days, or weeks (i.e., chronic hyponatremia), a gradual, conservative approach is likely to be uncomplicated Symptomatic chronic hyponatremia, on the other hand, requires a small but rapid increase in serum sodium to stabilize or begin to reverse cerebral swelling and to avoid impending herniation, followed by a more gradual correction to normalize sodium balance An increase of mEq/L is usually sufficient to halt the progress of symptomatic cerebral edema and can be achieved with an initial bolus of to mL/kg of 3% saline The subsequent correction rate for patients with either acute symptomatic hyponatremia or any chronic hyponatremia should not exceed 0.5 mEq/L per hour In acute hyponatremia without CNS symptoms, rates of 0.7 to mEq/L per hour have been reported without increased patient morbidity or mortality A regimen of hypertonic 3% saline infused at to mL/kg per hour with intermittent administration of a loop diuretic results in an appropriate correction for those patients for whom “rapid” correction is safe Further correction may require isotonic fluids or a mixture of isotonic and hypertonic fluids, particularly in patients with CSW with high renal sodium excretion In resistant, severe CSW, mineralocorticoid (fludrocortisone) treatment has been helpful in several reports.72,97,98 Other protocol approaches are available.99 Prolonged hyponatremia in animal studies is notable for a striking decrease in total brain amino acid content as well as lower brain water content.100 When this brain cell adaptation has occurred, a rapid rise in serum sodium concentration may induce a shift of water from the ICF to the ECF compartment, resulting in brain dehydration, brain injury, and the osmotic demyelination syndrome (ODS).101 Both central pontine and extrapontine myelinolysis have been reported in children.102–105 Extrapontine sites include the cerebellum, thalamus, basal nuclei, hippocampus, midbrain, and subcortical white matter.97 Traditional risk factors for ODS include chronic alcoholism, chronic liver disease, hypoxic/ anoxic episodes, correction beyond serum sodium of 140 mEq/L, and rapid correction of hyponatremia (more than 25 mEq/L in 48 hours).106,107 Osmotic demyelination can occur, however, without hyponatremia as a starting point.104,105,108 Large bolus doses of hypertonic saline may place the patient at risk regardless of starting sodium concentration Electrolyte fluctuations around the time of liver transplantation may account for the risk of myelinolysis noted in these patients.109 Rarely, ODS has been reported in patients with diabetic ketoacidosis but without hyponatremia on admission, including one case in an 18-month-old child.103,105 Even rapid correction of hypernatremia is a possible cause of myelinolysis and suggests that pressure effects may be capable of causing damage to myelinated structures Symptoms of osmotic demyelination may include obtundation, quadriplegia, pseudobulbar palsy, tremor, amnesia, seizures, and coma.110,111 Classically, the clinical presentation is that of a brief period of recovery from encephalopathy followed by emergence of a lockedin state or various movement disorders.106 When CNS symptoms concerning for ODS emerge during therapy, long-term neurologic sequelae may be avoided by decreasing serum sodium to its nadir followed by a slower rate of correction.112–114 In cases of SIADH in which fluid restriction is a feasible option, a decrease in fluid intake, occasionally with the use of oral sodium supplements, may be all that is required to normalize serum sodium gradually and safely In a patient with hypovolemia, volume status clearly must be corrected in addition to the hyponatremia Patients with SIADH or fluid-retaining states may respond to treatment with an ADH receptor antagonist This receptor blocker group increases urine volume and reduces urine osmolality, creating a water diuresis that leads to an increase in serum sodium concentration.115,116 However, evidence for improvement in other clinical outcomes, such as mortality or ICU LOS, is currently lacking Conivaptan is an IV ADH V1 and V2 receptor antagonist that is approved for the treatment of euvolemic and hypervolemic hyponatremia in adults.117 Tolvaptan, an oral ADH V2 receptor antagonist, was approved in 2009 as therapy for euvolemic or hypervolemic hyponatremia in adult patients with heart failure, cirrhosis, or SIADH.116 Pediatric use of the ADH receptor blockers has been reported in the settings of SIADH and cardiac disease,116–120 but further study of kinetics, safety, and efficacy will be needed to clarify the clinical role in pediatrics Hypernatremia As with hyponatremia, hypernatremia can develop with low, normal, or high levels of total body sodium (eBox 71.3) History and weights are particularly important in evaluating the hydration state of patients with hypernatremia because a shift in the ICF to the ECF tends to obscure the physical findings of dehydration Accurate assessment of total body sodium and water aids considerably in planning management, although the most important management principle is the frequent monitoring of the patient’s progress with treatment adjustments as needed 870.e1 • eBOX 71.3 Causes of Hypernatremia Decreased Total Body Sodium Extrarenal Vomiting/diarrhea, excessive sweating Administration of 70% sorbitol Renal Osmotic diuresis: mannitol, glucose, urea Inadequate Intake Insufficient lactation Normal Total Body Sodium Extrarenal Respiratory insensible water losses Cutaneous insensible water losses Fever, burns, phototherapy Radiant warmers, especially with premature infants Renal Diabetes insipidus (DI) Central DI Nephrogenic DI Hypodipsia (reset osmostat) Increased Total Body Sodium Administration or ingestion of large sodium loads Improperly diluted formula CHAPTER 71 Fluid and Electrolyte Issues in Pediatric Critical Illness Pathophysiology and Etiology Low Total Body Sodium Patients with a low total body sodium level and hypernatremia have a loss of water in relative excess of sodium losses Because the ECF space is hyperosmolar, water movement from the ICF occurs, with resulting cellular dehydration Therefore, the ECF space is somewhat preserved until an extreme degree of hypovolemia is present Losses of sodium and water may be extrarenal or renal In the pediatric patient, extrarenal losses are commonly seen from vomiting and diarrhea, although hospital-acquired hypernatremia from insufficient free water administration is a major concern.121,122 Renal causes include osmotic diuresis from mannitol, hyperglycemia, or increased urea excretion Infants are particularly susceptible to hypernatremic dehydration due to their high surface area/weight ratio and their relative renal immaturity, which necessitates greater water losses for excretion of a solute load compared with older children and adults.123 Insufficient maternal lactation places young infants at risk of hypernatremic dehydration Normal Total Body Sodium Loss of water occurs without excessive sodium losses in some conditions Extrarenal losses include (1) increased respiratory losses as may occur with tachypnea, hyperventilation, or mechanical ventilation with inadequate humidification and (2) transcutaneous losses associated with fever, burns, extreme prematurity, or use of phototherapy or radiant warmers in the neonate without adequate water replacement Renal losses result from congenital or acquired diabetes insipidus (DI), either central or nephrogenic Acquired forms of DI are more commonly seen in the ICU Major insults resulting in central DI include head trauma, tumors, infections, hypoxic brain injury, neurosurgical procedures, and nontraumatic brain death Classically, in experimental animals and in humans, three stages occur: (1) an initial polyuric phase (hours to several days), (2) a period of antidiuresis probably due to ADH release from injured axons (hours to days), and (3) a second period of polyuria that may or may not resolve.124,125 Sudden onset of polyuria is characteristic, and the conscious patient will often experience a concomitant polydipsia In the critically ill patient, the inability to access increased water intake—whether from altered mental status, impaired thirst regulation, or other causes—may result in life-threatening hypernatremia.126 Patients with the rare congenital forms of nephrogenic DI, resulting from X-linked alteration of the ADH V2 receptor or from autosomal recessive changes in the aquaporin II water channel itself, may have repeated bouts of hypernatremic dehydration.127 Causes of DI are shown in eBox 71.4 Increased Total Body Sodium Hypernatremia with an increased total body sodium level is most often an iatrogenic problem In the ICU, hypertonic solutions of sodium bicarbonate are administered during resuscitation efforts or as therapy for intractable metabolic acidosis Additionally, excessive hypertonic saline administration, ingestion by infants of improperly diluted formula, and dialysis against a high sodium concentration can contribute to increased total body sodium Normonatremic patients with massive edema who undergo a forced diuresis frequently become mildly hypernatremic because the induced urine may be hypotonic, with water loss exceeding sodium loss 871 Hypernatremia is intentionally induced in patients with TBI as a form of osmotherapy for control of intracranial hypertension associated with cerebral edema.128,129 Such patients have tolerated serum sodium as high as 175 mEq/L when carefully managed When the ECF osmolality of these patients is manipulated, the risks involved with rapid changes in either direction must be kept in mind Signs and Symptoms Clinical manifestations of hypernatremia, as is the case with hyponatremia, relate predominantly to the CNS Marked irritability, a high-pitched cry, altered sensorium varying from lethargy to coma, increased muscle tone, and overt seizure activity may occur in children with the development of severe hypernatremia over 48 hours or more Hyperglycemia and hypocalcemia also may occur In infants with acute hypernatremia, vomiting, fever, respiratory distress, spasticity, tonic-clonic seizures, and coma are common Death from respiratory failure occurred in experimental animals when serum osmolality approached 430 mOsm/kg.130 Mortality in children with severe hypernatremia has ranged from 10% to 45% with chronic and acute hypernatremia, respectively Anatomic changes seen with the hyperosmolar state include loss of volume of brain cells with resultant tearing of cerebral vessels, capillary and venous congestion, subcortical or subarachnoid bleeding, and venous sinus thrombosis During the first hours of experimental acute hypernatremia, brain water significantly decreases, while the concentration of solutes (electrolytes and glucose) increases.131 This leads to a partial restitution of brain volume within a few hours’ time Over several days, brain volume normalizes as a result of intracellular accumulation of organic osmolytes consisting of polyols, amino acids, and methylamines.125,132 Treatment Whenever possible, therapy of hypernatremia should address correction of the underlying disease process as a primary goal Correction of dehydration with slow hypernatremia correction is the target When sodium exceeds 165 mEq/L, isotonic fluid or colloid may be used for correction of shock or circulatory collapse and initial reversal of hypernatremia When hypernatremia has been present for more than a few hours, the presence of intracellular organic osmolytes dictates a slow rate of correction Numerous fatal cases of cerebral edema and herniation have occurred with correction over a 24-hour period, leading to recommendations for correction over no less than 48 hours.133,134 Newer studies suggest that rapid correction of hypernatremia is not associated with higher risk for mortality, seizure, or cerebral edema in critically ill adults94,135; therefore, the ideal rate of correction remains unclear General agreement is that plasma osmolality should not be decreased more rapidly than mOsm/h, correlating with a rate of sodium decline that does not exceed mEq/h In cases of very severe or long-standing hypernatremia, a more conservative correction rate of mOsm/h (0.5 mEq/h of sodium) may be appropriate Thus, normalization from extreme hypernatremia may take several days Estimated deficits, ongoing maintenance requirements, and additional excessive losses must be accounted for in calculations of the amount of fluid replacement required Central DI is a likely cause of hypernatremia in an ICU patient with high urine volume and low urine osmolality, particularly in patients who have head trauma or who have undergone a 871.e1 • eBOX 71.4 Causes of Diabetes Insipidus Central Congenital Arginine vasopressin, antidiuretic hormone, gene mutations, autosomaldominant or (rarely) autosomal-recessive inheritance Idiopathic (30%–50% of cases) Acquired Head trauma, orbital trauma Tumors, suprasellar and intrasellar Encephalitis Meningitis Guillain-Barré syndrome Hypoxic injury, including neonatal hypoxic-ischemic encephalopathy Postneurosurgical procedures Cerebral aneurysms, thrombosis, hemorrhage Histiocytosis Granulomas Nontraumatic brain death Nephrogenic Congenital VR2 mutation, X-linked AQP-2 mutation Acquired Chronic kidney disease Renal tubulointerstitial diseases Hypercalcemia K1 depletion Drugs Alcohol, lithium, diuretics, amphotericin B, methoxyflurane, demeclocycline Sickle Cell Disease Dietary Abnormalities Primary polydipsia Decreased sodium chloride intake Severe protein restriction or depletion ... the concentration of solutes (electrolytes and glucose) increases.131 This leads to a partial restitution of brain volume within a few hours’ time Over several days, brain volume normalizes as... Patients with SIADH or fluid-retaining states may respond to treatment with an ADH receptor antagonist This receptor blocker group increases urine volume and reduces urine osmolality, creating a water... patient, the inability to access increased water intake—whether from altered mental status, impaired thirst regulation, or other causes—may result in life-threatening hypernatremia.126 Patients with