872 SECTION VII Pediatric Critical Care Renal recent intracranial operation In these patients, a trial of vasopres sin is in order Either aqueous vasopressin given subcutaneously or intravenously (0 5[.]
872 S E C T I O N V I I Pediatric Critical Care: Renal recent intracranial operation In these patients, a trial of vasopressin is in order Either aqueous vasopressin given subcutaneously or intravenously (0.5 to 10 mU/kg per hour) or 1-deamino-8-Darginine vasopressin (DDAVP) given orally or intranasally may be used Oral dosing is limited to tablet form at this time with a recommended dosing range of 0.05 to 0.40 mg administered twice daily Intranasal DDAVP is generally begun in a dosage ranging from 0.05 to 0.10 mL once or twice daily An increase in urine osmolality to values exceeding that of the serum after vasopressin administration supports the diagnosis of central DI Hyponatremia has been reported after vasopressin administration in patients with central DI as well as in patients receiving vasopressin for hemodynamic support and for bleeding disorders in the perioperative period.136,137 In the outpatient setting, symptomatic hyponatremia, including seizures and altered mental status, has been reported in patients receiving DDAVP for enuresis, particularly in periods of intercurrent illness or with excess fluid intake.138 Careful attention to the IV fluid prescription, serial monitoring of sodium levels, and timely adjustment in therapy are necessary to avoid severe complications in patients receiving any type of vasopressin therapy In patients with an increased total body sodium level and, often, hypervolemia, the goal is sodium removal In patients with intact renal function, sodium removal may be accomplished with diuretics and a decrease in sodium administration, though in iatrogenic hypernatremia, a randomized controlled trial did not find any significant improvement in serum or urine sodium with use of enteral hydrochlorothiazide.139 If renal failure is present, dialysis may be required Potassium The total body K1 of approximately 50 mEq/kg is stored primarily (98%) in the intracellular space The transmembrane concentration gradient is large, with an intracellular concentration of 150 mEq/L that is maintained by sodium-potassium adenosine triphosphatase (Na1/K1-ATPase) pumps The resultant transmembrane potential is tightly regulated and physiologically dynamic in contractile or conductive cells Changes in extracellular or intracellular K1 concentration may alter the critical transmembrane potential of cardiac, skeletal, or smooth muscle cells with serious results Hypokalemia is relatively common in pediatric intensive care unit (PICU) patients but generally is detectable and manageable.140 Severe hyperkalemia is much less frequent but more likely to be life threatening with minimal warning Potassium balance is primarily regulated through renal absorption and excretion and to a lesser extent by the gastrointestinal (GI) tract Most of the filtered potassium is absorbed in the proximal tubule and loop of Henle in normal kidneys The potassium excreted in the urine then is primarily due to secretion in the distal convoluted tubule and cortical collecting duct As with sodium, the kidney’s capacity to vary potassium excretion is profound, ranging from a low of approximately mEq/L to amounts exceeding 100 mEq/L of urine Factors influencing renal potassium excretion include aldosterone and other mineralocorticoid and glucocorticoid hormones, acid-base balance, luminal charge potential, tubular fluid flow rate, sodium intake, potassium intake, ICF and plasma potassium concentrations, and diuretics.141 Aldosterone is a major kaliuretic hormone though activation of Na1/K1 exchange pumps in the distal tubules and collecting ducts Metabolic acidosis decreases and metabolic alkalosis increases intracellular potassium activity in cells of the distal tubule, causing enhanced potassium reabsorption during acidosis and enhanced secretion during alkalosis Increased fluid delivery to the distal tubule enhances potassium secretion by two mechanisms: (1) increased distal delivery of Na1 stimulates distal Na1 absorption, which then creates a more negative luminal potential that increases K1 secretion; and (2) as tubular fluid potassium concentration decreases as flow rate increases, a favorable concentration gradient for potassium secretion is promoted by higher flow rates.142 Factors involved in total body distribution and fine-tuning of potassium homeostasis include acid-base status, insulin, catecholamines, and magnesium.143–146 Acidemia tends to increase the serum potassium, and alkalemia lowers it The type of acid–base disturbance (metabolic or respiratory), the duration of the disturbance, and the nature of the anion accompanying the hydrogen ion in metabolic acidosis are important in determining what effect a particular acid-base disorder may have on potassium concentration Diabetic ketoacidosis (DKA) may occasionally present with severe hypokalemia147 due to urinary and gastrointestinal losses; however, pretreatment serum levels can be normal or elevated due to acidemia, hyperosmolality, and decreased circulating insulin.148,149 Epinephrine, albuterol,150 and other b-agonists decrease serum potassium by promoting intracellular uptake b-Adrenergic blocking drugs abolish this effect Changes in intracellular magnesium concentration may affect the Na1/K1-ATPase pump and alter the transcellular distribution Causes of Hypokalemia Hypokalemia Without Potassium Deficit The detection of a low serum potassium level may reflect a shift of K1 from the ECF to the ICF pool and not a whole-body K1 deficit A shift to the ICF pool may occur in alkalemia,151 exogenous or endogenous release of a b-agonist,150,152 increased insulin activity familial or thyrotoxic periodic paralysis,153,154 and barium poisoning.155 In alkalemia, potassium moves intracellularly in exchange for H1 to maintain extracellular pH The pediatric patient with alkalemia can have a true potassium deficit in addition due to decreased potassium intake or increased losses b-Agonists and insulin promote intracellular potassium movement by increasing the activity of the Na1/K1-ATPase pump Periodic paralysis is a rare autosomal-dominant disorder presenting with intermittent episodes of profound muscle weakness associated with rapid falls in serum potassium concentration that may be precipitated by a high-carbohydrate diet, exercise, infection, stress, or alcohol ingestion Barium poisoning can produce hypokalemic weakness and paralysis, probably by competitive blockade of inward rectifying K1 channels Hypokalemia With Potassium Deficit A deficit in total body potassium may occur from decreased intake or increased renal and GI losses Decreased intake is unlikely to cause significant hypokalemia in isolation, though prolonged deficits can exacerbate hypokalemia due to increased losses Renal Losses ajor categories seen in the ICU include diuretics (loop, thiaM zide, osmotic), hyperaldosteronism, renal tubular acidosis (RTA), magnesium deficiency, renal tubular injury, and recovery from acute renal failure (ARF) Osmotic diuresis from glucosuria in prolonged DKA can cause severe renal potassium wasting DKA The severity of K1 loss in DKA may be masked by the shift CHAPTER 71 Fluid and Electrolyte Issues in Pediatric Critical Illness of potassium from the ICF to the ECF space caused by insulin deficiency, metabolic acidosis, and hypertonicity Primary hyperaldosteronism, congenital adrenal hyperplasia, adrenal adenoma, and familial idiopathic hyperaldosteronism156,157 are rare in children and even rarer in the PICU setting Secondary hyperaldosteronism is common, however, typically from intravascular volume depletion but also caused by CHF, cirrhosis, or nephrotic syndrome Patients with the latter conditions, however, rarely have severe hypokalemia unless they are additionally treated with diuretics Infants with Bartter or Gitelman syndrome158 may initially present to the ICU with multiple metabolic derangements, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hyperuricemia Other findings include weakness, polyuria, and failure to thrive, with elevated renin and aldosterone levels in the absence of hypertension Additional conditions associated with elevated renin secretion, secondary hyperaldosteronism, and hypokalemia include renal artery stenosis, malignant hypertension, renin-producing tumor, or Wilms tumor Distal (type 1) RTA represents impaired distal urine acidification, which increases urinary potassium secretion, while proximal (type 2) RTA causes increased distal delivery of sodium bicarbonate secondary to reduced proximal absorption, which may increase urinary secretion of K1 Other agents that induce excessive renal losses include amphotericin B (kaliuresis with reduced renal function and tubular injury); aminoglycosides, particularly gentamicin; and high-dose penicillin and carbenicillin, which produce an osmotic load in addition to acting as nonreabsorbable anions Hypomagnesemia and caffeine toxicity may cause renal potassium wasting.159–161 Gastrointestinal Losses astrointestinal losses are a common cause of hypokalemia in G children Stool potassium content can be significant162 and diarrheal illness with hypokalemia has been associated with increased mortality among malnourished patients.163 Gastric potassium content ranges from to 10 mEq/L Hypokalemia from vomiting or from nasogastric (NG) suction is possible However, hypokalemia from upper GI losses is more likely due to the secondary hyperaldosteronism induced by volume depletion and metabolic alkalosis from hydrogen ion losses, which also causes an increased filtered load of bicarbonate that promotes increased renal potassium secretion Other GI causes are listed in eBox 71.5 Signs and Symptoms For the intensivist, cardiovascular and neuromuscular effects of potassium deficiency are of particular concern, although metabolic, hormonal, and renal effects may also occur Electrocardiographic (ECG) changes include T-wave flattening or inversion, ST depression, and the appearance of a U wave Resting membrane potential is increased, as are both the duration of the action potential and the refractory period The decreased conductivity predisposes to arrhythmias, as increased threshold potential and automaticity.164 Hypokalemia diminishes skeletal muscular excitability This can present as a dynamic ileus or a skeletal muscle weakness resembling Guillain-Barré syndrome It can eventually affect the trunk and upper extremities, becoming severe enough to result in quadriplegia and respiratory failure.165 Hypokalemia can lead to severe rhabdomyolysis in a variety of underlying conditions166–169 and may progress to ARF and hyperkalemia.170 Autonomic insufficiency may also occur, generally manifested as orthostatic hypotension In patients 873 with severe liver disease, hypokalemia may precipitate or exacerbate encephalopathy Glucose intolerance in the presence of primary hyperaldosteronism and in certain patients receiving thiazide diuretics has been corrected with potassium repletion Renal effects of hypokalemia include polyuria and polydipsia, renal structural changes and functional deterioration with cellular vacuolization in the proximal tubule, and occasional interstitial fibrosis Treatment Because of the wide spectrum of abnormalities resulting from marked potassium depletion, judicious correction is generally in order In most PICUs, patients with cardiovascular disease are given NG or IV supplements to maintain serum levels above 3.0 to 3.5 mEq/L In the patient without life-threatening complications, the oral route is generally preferred for treatment because this route is rarely associated with “overshoot” hyperkalemia if normal renal function exists Oral dosage is frequently mEq/kg up to a maximum of 20 mEq per dose, repeated as necessary If, however, depletion is associated with digoxin use or life-threatening complications—including cardiac arrhythmias, rhabdomyolysis, critical weakness with quadriplegia, or respiratory distress—then urgent IV therapy is generally needed Recommendations for IV dosage in the pediatric patient have ranged from intermittent infusions of 0.25 mEq/kg to those as high as mEq/kg in the face of severe hypokalemia associated with DKA, arrhythmias, or critical weakness Ventricular tachycardia clearly associated with hypokalemia may initially require more rapid administration Continuous ECG monitoring is essential, as well as frequent physical examination and determination of serum potassium levels to avoid hyperkalemic complications Highly concentrated intravenous potassium solutions should only be administered centrally Patients who receive albuterol continuously are frequently mildly hypokalemic, but they rarely warrant potassium chloride replacement The potential for catastrophic drug error in replacing potassium is real In most PICUs, patients with cardiovascular disease frequently require NG or IV supplements Steps to decrease the chance of error include satellite pharmacy dosing, use of a mandatory drug request form, NG replacement when possible, use of a single-solution concentration for all doses, and small aliquot solution containers Continuing education for the PICU staff regarding this risk is essential Hyperkalemia Causes Hyperkalemia may result from artifactual elevation; from redistribution of potassium from ICF to ECF space; or from increased load, impaired elimination, or both (eBox 71.6) Artifactual Tight, prolonged tourniquet use produces spurious potassium elevation due to potassium release from ischemic muscle Even more common is hemolysis of red cells with potassium release associated with capillary sampling, and aspiration or delivery under pressure through a small gauge needle The lab may note hemolysis, but artifactual normality or actual elevation should always be considered.171 Less commonly, in vitro release of potassium occurs from white blood cells (WBCs; 100,000/uL) or platelets (.1,000,000/uL) and may result in increased levels 873.e1 • eBOX 71.5 Causes of Hypokalemia • eBOX 71.6 Causes of Hyperkalemia Hypokalemia Without Potassium Deficit Artifactual Alkalosis b-agonist, exogenous or endogenous Familial periodic paralysis Thyrotoxic periodic paralysis Barium poisoning Excessive insulin Ischemic potassium loss from muscle due to tourniquet use In vitro hemolysis, profound leukocytosis, thrombocytosis Hypokalemia With Potassium Deficit Decrease intake Renal losses Hyperaldosteronism Primary or secondary Barter, Liddle, Gitelman syndromes Laxative or diuretic abuse Licorice ingestion Osmotic agents Drugs Caffeine Diuretics Amphotericin B Aminoglycosides High-dose penicillin, carbenicillin Miscellaneous Hypomagnesemia Renal tubular acidosis Toluene toxicity Extrarenal Losses Gastrointestinal Vomiting, nasogastric suction Diarrhea Laxative abuse Ureteral sigmoidostomy Obstructed or long ileal loop Drugs Digoxin toxicity b-blockers (b2-inhibitory activity) Succinylcholine, arginine, or lysine hydrochloride Chemotherapeutic agents Sodium fluoride Epsilon-amino caproic acid True Potassium Excess Increased Load IV infusion, PO supplements, potassium-containing salt substitutes, potassium penicillin, blood transfusion Redistribution and Tissue Necrosis In vivo red cell injury Change in pH Hypertonicity Burns, trauma, rhabdomyolysis, intravascular coagulation Gastrointestinal bleeding Tumor cell lysis Reabsorption of hematoma Diabetes mellitus, diabetic ketoacidosis Decreased Excretion Acute kidney injury Chronic kidney disease Mineralocorticoid deficiency Addison disease 21-Hydroxylase deficiency Desmolase deficiency 3-b-OH-dehydrogenase deficiency Renal tubulointerstitial disease Renal Tubular Secretory Deficit Pseudohypoaldosteronism Sickle cell disease Systemic lupus erythematosus Renal allograft rejection Urinary tract obstruction Very-low-birth-weight infants Inhibition of Tubular Secretion Drugs Spironolactone, triamterene, amiloride Indomethacin, converting enzyme inhibitors, heparin, cyclosporine, tacrolimus Trimethoprim, pentamidine, amphotericin B 874 S E C T I O N V I I Pediatric Critical Care: Renal Redistribution In general, when extracellular pH acidemia develops, potassium exits from cells in exchange for hydrogen ions; this results in an increase in serum potassium Metabolic acidosis from mineral acids has a more pronounced effect than that of organic acids Respiratory acidosis does not usually cause a marked change in potassium concentration Hypertonicity produces a shift of potassium from ICF to ECF Studies of anephric animals show potassium increasing by 0.1 to 0.6 mEq/L for each increment of 10 mOsm/kg H2O in tonicity Hypertonicity causes cellular dehydration and therefore an increase in ICF potassium that favors increased passive diffusion out of cells A very small percentage shift of intracellular potassium delivers a significant potassium load to the ECF In the hyperkalemic patient in the ICU who has acute oliguria, mannitol should not be used for diuresis, as further K1 elevation may result.172 In the patient with hyperglycemia, hypertonicity is likely only one of several mechanisms resulting in elevated serum potassium levels Several commonly used drugs result in net movement of potassium from ICF to ECF Digoxin inhibits the net uptake of K by cells by inhibiting Na1/K1-ATPase activity, with hyperkalemia commonly occurring in severe digitalis poisoning.173 Other drugs include b-blockers with b2 activity and the muscle relaxant succinylcholine Succinylcholine induces a prolonged dose-related increase in the ionic permeability of muscle, with subsequent efflux of potassium from muscle cells Normal serum potassium concentration rises about 0.5 mEq/L Succinylcholine should be avoided in patients with burns, muscle trauma, spinal injuries, certain neuromuscular diseases, near drowning, and closed head trauma, as upregulated and new forms of acetylcholine receptors may respond with life-threatening hyperkalemia.172,174 New examples of patients at risk will continue to be reported.175,176 Hyperkalemia may result in nonsuspect patients via rhabdomyolysis or malignant hyperthermia following succinylcholine Rhabdomyolysis has many causes, including influenza, severe exercise, drugs, ischemia, and many more.177–179 Familial hyperkalemic periodic paralysis appears to be related to potassium redistribution caused by changes in sodium channel function within skeletal muscle Rebound hyperkalemia may be life threatening after coma-inducing barbiturate is stopped or surgical insulinoma removal Increased Load Hyperkalemia due to an increased potassium load is unusual as long as renal function is normal Serious elevations may be seen with inappropriate IV infusion, large-volume blood transfusions,180 bypass circuit initiation,181 oral potassium supplements, salt substitutes containing potassium, or large doses of potassium penicillin Strict measures to guard against accidental potassium overdoses are mandatory.182 Large endogenous loads of potassium are more likely in the patient who is in the ICU The release of cellular potassium associated with tissue necrosis from burns, trauma, rhabdomyolysis (including that from spider bites)183 or the propofol infusion syndrome,184,185 massive intravascular coagulopathy, rapid hemolysis, or GI bleeding may lead to hyperkalemia Massive cell lysis can overwhelm normal homeostasis, prompting aggressive management of the sudden shift of intracellular potassium into the ECF, particularly in the presence of compromised renal function Tumor lysis syndrome (TLS) is classically associated with drug or radiation treatment of sensitive lymphoid malignancies and results in hyperkalemia often accompanied by hypocalcemia, hyperphosphatemia, acidosis, and compromised renal function TABLE Tumor Lysis Syndrome 71.3 High risk Lymphoid malignancies, large tumor mass, B-cell lymphoma concurrent renal compromise Initiating event Cytolytic chemotherapy Radiation therapy Embolic tumor infarction Prophylaxis Hydration, urinary alkalinization, allopurinol Gradual chemotherapy initiation, rasburicase Serious disturbances Hyperkalemia, hypocalcemia, acidosis, acute kidney injury, hyperuricemia, hyperphosphatemia Management Obsessive electrolyte monitoring, hemodialysis available stat, continuous venovenous hemodialysis helpful, may not be adequate (Table 71.3).186 Many fatalities have been reported The list of TLS-producing events or therapies includes transcatheter chemical and embolic tumor necrosis, monoclonal antibody treatment with rituximab, and enzyme-inhibiting agents (bortezomib, imatinib, and sorafenib) Cases have occurred in tumor patients with surgical stress or dexamethasone given for potential airway edema (see also Chapter 92) Impaired Elimination Persistent hyperkalemia implies impaired renal elimination The decreased GFR and urine flow seen in acute and chronic kidney disease leads to decreased distal delivery of Na1 and subsequent decreased K1 excretion Several medications, such as potassiumsparing diuretics, calcineurin inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), calcium channel blockers, angiotensinconverting enzyme inhibitors, and angiotensin receptor inhibitors can decrease urinary potassium excretion through alterations in the RAAS.187 Serum potassium values should be monitored closely when administering these medications to patients with comorbidities associated with hyperkalemia, such as renal failure and heart failure.188 Other alterations in the RAAS that promote hyperkalemia include hypoaldosteronism (primary, secondary, type RTA), pseudohypoaldosteronism, and congenital adrenal hyperplasia due to 21-hydroxylase deficiency.189 Manifestations of Hyperkalemia Life-threatening complications are most likely to result from the cardiac changes caused by hyperkalemia ECG signs include tall, peaked T waves in the precordial leads, followed by a decrease in amplitude of the R wave, bradycardia, widened QRS complexes, prolonged PR intervals, and decreased amplitude and disappearance of the P wave.190 Finally, the classic sine wave of hyperkalemia from the blending of the QRS complex with the P wave may appear ECG changes not necessarily correlate with specific levels of serum potassium.191 Ventricular arrhythmias or cardiac arrest may occur at any point in this progression and the progression may be rapid CHAPTER 71 Fluid and Electrolyte Issues in Pediatric Critical Illness Treatment Treatment of hyperkalemia depends on the level of plasma potassium and the state of cardiac irritability.192 If the potassium concentration is more than 6.5 mEq/L with associated ECG changes, additional measures are indicated In the absence of digitalis toxicity, hyperkalemia with ECG changes should be treated with a secure and rapid IV infusion of calcium chloride or calcium gluconate Hand injection with ECG monitoring is reasonable, beginning with the administration of 10 to 20 mg/kg of calcium chloride (or gluconate equivalent) over to minutes Infusion may be stopped if the electrocardiogram has normalized or if deterioration of the electrocardiogram seems to be precipitated by the potassium, suggesting a clinical scenario more complex than simple hyperkalemia If the electrocardiogram improves but is not normalized by this calcium dose, additional calcium chloride may be given at a lower rate It should be anticipated that ECG changes will recur in 15 to 30 minutes unless additional measures are taken immediately to treat the hyperkalemia The effective calcium dose may be repeated as necessary to preserve cardiac function while additional treatments are in progress Additional, rapidly effective treatments include nebulized albuterol (rapid neb or continuous neb of 0.3– 0.5 mg/kg) or, among neonates, salbutamol (IV dose of 4–5 µg/kg over 20 minutes and repeated after hours).192,193 Insulin and glucose are also helpful in rapidly redistributing potassium to the ICF Glucose (0.5 to g/kg) and insulin (0.2 U/g glucose) may be given over 15 to 30 minutes and then infused continuously with a similar amount per hour A premixed combination glucose and insulin solution has been successfully demonstrated in a 21-patient series.194 Blood glucose monitoring is essential because the relative glucose and insulin amounts may need adjustment Sodium bicarbonate (1–2 mEq/kg given IV) has been a part of the classic treatment of hyperkalemia However, its benefit is more difficult to predict and slower in onset than that of the measures mentioned earlier Sodium polystyrene sulfonate removes potassium and may be administered while dialysis arrangements are made Sodium polystyrene sulfonate administered rectally must be retained for 15 to 30 minutes to be effective If the oral route is available, it is generally more efficient Hemodialysis is the treatment of choice for removal of potassium in emergent conditions In the patient with severely compromised renal function, the measures discussed earlier generally allow stabilization of potassium long enough to institute dialysis Although hemodialysis is much more efficient for potassium removal than peritoneal dialysis, the latter may be more quickly instituted in many centers, particularly in the small infant in whom vascular access to support reasonable blood flow may be difficult to accomplish In the absence of renal failure, loop diuretics or thiazide diuretics or both are useful for the increase of renal excretion If mineralocorticoid activity is deficient, the administration of fludrocortisone may be indicated In patients with severe hyperglycemia and moderate hyperkalemia, early steps to improve glucose control should decrease ECF potassium shifts from hyperosmolality and decreased insulin If the potassium is less than 6.5 mEq/L without ECG changes, discontinuation of exogenous potassium and drugs that decrease its excretion with close follow-up of potassium levels may be all that is necessary In the patient with renal compromise, extra potassium may be eliminated with use of the potassium-binding agent sodium polystyrene sulfonate (Kayexalate, resonium [oral, NG, or rectal doses of g/kg in a sorbitol or dextrose solution]) 875 When administered rectally, sorbitol may not be necessary, and it should certainly not be given rectally in concentration greater than 20% Highly concentrated sorbitol may cause severe proctitis and colonic injury Increasing reports of colonic injury, particularly in hemodynamically compromised or premature patients, suggest that caution should be exercised in using this preparation However, when needed, having the pharmacy stock a premixed 10% to 20% suspension of sodium polystyrene sulfonate and sorbitol allows either oral or rectal administration on short notice Magnesium Magnesium plays a key role in numerous metabolic processes, including cellular energy production, storage, and utilization involving ATP; the metabolism of protein, fat, and nucleic acids; and the maintenance of normal cell membrane function It is also involved in neuromuscular transmission, cardiac excitability, and cardiovascular tone.195 Magnesium balance is maintained through intestinal absorption and renal excretion; 25% to 65% of ingested magnesium is absorbed in the ileum Absorption varies inversely with intake and is also affected by paracellular water reabsorption Increased bowel water from any cause results in decreased magnesium absorption Regulation of renal excretion occurs by glomerular filtration and reabsorption The majority of filtered magnesium is reabsorbed in the ascending limb of the loop of Henle, resulting from active NaCl reabsorption and susceptible to loop diuretic inhibition The threshold value for magnesium excretion varies between 1.5 and mg/dL in different species Thus, if serum magnesium levels fall even slightly, renal excretion dramatically decreases under normal circumstances Decreased excretion occurs with ECF volume depletion, hypomagnesemia, hypocalcemia, hypothyroidism, and, to a lesser extent, metabolic alkalosis Parathyroid hormone (PTH) may decrease magnesium excretion, but that effect may be offset by the opposite effect of causing hypercalcemia Primary factors that increase renal magnesium excretion include ECF volume expansion; hypermagnesemia; hypercalcemia; metabolic acidosis; phosphate depletion; and various drugs, including loop and osmotic diuretics, cisplatin, aminoglycosides, cyclosporin, and digoxin Hypomagnesemia Measurement of total serum magnesium is clinically effective for determining magnesium status, with the measurement of free (ionized) magnesium not proven to be of clinical utility.196 Evidence supporting obligatory ionized magnesium measurement remains elusive.197 Hypomagnesemia is common in critically ill patients with sepsis and needs to be identified and corrected given its association with morbidity and mortality.198 Magnesium depletion may result in hypocalcemia via suppression of PTH secretion Hypokalemia also occurs in patients with hypomagnesemia Magnesium deficiency impairs the Na1/K1 pump, allowing potassium loss from the ICF to the ECF and urinary excretion Magnesium repletion is important to resolve secondary disturbances of hypocalcemia and hypokalemia Causes Intensivists deal with hypomagnesemia most often in patients receiving loop diuretics or transplant immunosuppressive drugs, though other causes must be considered.199 ... Primary hyperaldosteronism, congenital adrenal hyperplasia, adrenal adenoma, and familial idiopathic hyperaldosteronism156,157 are rare in children and even rarer in the PICU setting Secondary... threshold potential and automaticity.164 Hypokalemia diminishes skeletal muscular excitability This can present as a dynamic ileus or a skeletal muscle weakness resembling Guillain-Barré syndrome... Glucose intolerance in the presence of primary hyperaldosteronism and in certain patients receiving thiazide diuretics has been corrected with potassium repletion Renal effects of hypokalemia include