Introduction

Although based on long standing historical fluid calculation requirements, the routine use of five percent dextrose in half normal saline in surgical patients may be dangerous.

What is the effect of inappropriate fluid management in the pediatric patient?

In pediatric surgical patients, fluid administration is necessary to maintain adequate tissue perfusion and cellular metabolism. While the body has several stress-related mechanisms to maintain intravascular volume in the peri-operative period (e.g. antidiuretic hormone secretion), these are often insufficient by themselves. Indeed, fluid is often required to acutely replete gastrointestinal, renal, or blood losses as well as to compensate for insensible losses secondary to fever, hyperventilation, or increased metabolism.

Calculating the fluid and electrolyte requirements of pediatric patients has been based on the Holliday and Segar method since the 1950s [1] (see Medical Treatment) The Holliday and Segar method also approximated the daily electrolyte requirement of 2 mEq/100 mL/kg and 3 mEq/100 mL/kg for potassium/chloride and sodium, respectively.

These fluid and electrolyte calculations are the basis of selection of D₅ 0.45 NaCl as the most commonly used intravenous fluid in ill children. This solution, while generally appropriate for fluid replacement in the unstressed child, does not meet the electrolyte requirements following major surgery or injury. D₅ 0.45 NaCl contains only 77 mEq/L of sodium and is thus hypotonic with respect to plasma sodium concentrations. In addition, this solution only provides 20% of caloric requirements for unstressed children.

The use of D₅ 0.45 NaCl in surgical patients, based on the Holliday and Segar method, can lead to fluid overload in the extracellular compartment and dangerous electrolyte disturbances especially hyponatremia. Neurological impairment (e.g. encephalopathy, seizures) and death have been reported as a result of the extended use of hypotonic solutions, particularly in the context of suboptimal sodium surveillance [2]. Significant evidence has identified that the use of hypotonic fluid for maintenance and resuscitation doubles the risk of hyponatremia [3][4]. Furthermore, the use of isotonic fluids has not been associated with hypernatremia in hospitalized children [5]. The risk of hyponatremia is increased in children undergoing surgical procedures and may be related to the release of antidiuretic hormone [6]. The use of appropriate fluids in these patients thus becomes critically important.

Basic Science

Total body water makes up a larger percentage of body weight as age and gestation decrease. Despite a lower glomerular filtration rate, infants have a significant postnatal diuresis.

What is the normal body water composition in neonates and what fluid shifts take place in the newborn period?

Total body water (TBW) in a full term newborn comprises 75 to 80% of body weight and is divided into extra- and intracellular fluid compartments. Approximately 45% is in the extracellular compartment at birth. A shift from the intracellular compartment over the next two to three days leads to a diuresis (1 to 3 mL/kg) that results in a loss of 5 to 10% of the body weight. Over the next year, TBW reduces to 60% of body weight of which 20-25% is contained in the extracellular compartment (which is similar to adult levels) [7].

TBW is inversely related to gestational age, with a larger percentage (up to 85%) of TBW in more premature newborns. Similarly, the extracellular compartment is larger in premature infants and there is a greater diuresis (greater than 3 mL/kg) resulting in a greater drop in weight (up to 15%) in the first week of life [8]. This reflects the changes that normally occur in utero over the final six to eight weeks of gestation.

How does glomerular filtration rate, concentrating ability and sodium management in the kidney differ in the preterm and the full term newborn?

An obligatory diuresis occurs in both term and preterm infants despite the fact that the newborn kidney has a glomerular filtration rate (GFR) that is 25% of adult rates.[10] This low GFR is due to the low percentage of cardiac output that is directed towards the kidneys in the newborn. While adults normally direct 16% of their cardiac output to the kidneys, only two percent of the cardiac output is directed to the kidneys in newborns. This increases to 8.8% at five weeks and to 9.6% by the end of the first year [11]. Despite this low GFR, diuresis occurs since the infant can excrete very dilute urine (down to an osmolarity of 50 mOsm/kg in comparison to a maximal dilution of 70 to 100 mOsm/kg in adults) [10]. In addition, newborn kidneys are less adept at sodium retention due to limited Na-K-ATPase and Na-K exchange expression. The ability to retain sodium by the kidney is further limited in the premature infant but improves over time.

What are the insensible losses of the newborn and infant?

Fluid losses in the newborn period occur through the skin and the respiratory tract. Full term infants lose approximately 50 mL/kg/day through the skin and respiratory tract. The fluid loss through skin of premature and extremely low birth weight (ELBW) infants is higher than full term infants. Radiant warmers increase the losses [12]. Premature infants can easily lose in excess of 150 mL/kg/day in insensible losses if they are not in appropriate incubators in which humidity and ambient temperature are appropriately controlled. Approximately half the insensible losses in full term babies can occur through the respiratory system which are increased with reduced gestational age and increased respiratory rate [13][14].

Classification

How is renal insufficiency and acute kidney injury classified?

Renal failure has been reclassified as acute kidney injury (AKI) due to its potentially reversible course [15]. AKI can be primary or secondary based on whether it represents direct injury to the kidney or is the result of a systemic disease process that affects the renal interstitium or overall renal perfusion. AKI is manifest clinically by a decline in urine output (UO) and a simultaneous elevation in serum creatinine (Cr). These two clinical parameters, however, are often unreliable. A low UO does not necessarily correlate with the severity of renal dysfunction as is observed in nonoliguric renal failure or in patients receiving diuretics. Similarly, minor changes in Cr may not accurately reflect ongoing kidney injury since a loss >50% of functioning renal mass is needed to affect the serum Cr. Coexistent fluid overload in critically ill children with AKI may dilute Cr and falsely maintain it within normal reference ranges.

How does one determine whether the cause of acute kidney injury is prerenal, renal or postrenal?

Common causes of AKI include the following

• hypovolemia leading to reduced renal/glomerular perfusion
• medications or toxic metabolite-induced interstitial or tubular damage
• acute post-renal obstruction in urinary outflow

These three mechanisms represent prerenal, renal/intrinsic, and postrenal causes of AKI, respectively. In developed countries, only 10% of AKI is due to primary kidney disease (e.g. interstitial diseases such as renal dysplasia, renal hypoplasia and obstructive uropathy in young children and glomerular-based diseases such as glomerulonephritis in older children). The majority of cases are due to multifactorial causes associated with systemic illnesses, sepsis, cardiac surgery for congenital heart disease and nephrotoxic medications. In developing nations, hemolytic uremic syndrome is still the main cause of renal failure in children.

PrerenalAKI(renal/glomerular hypoperfusion)

In prerenal AKI, kidney injury results from hypoperfusion. The most common cause of hypoperfusion is hypovolemia due to severe dehydration, bleeding, gastrointestinal losses or major burns. Diminished renal perfusion can also occur with normal or elevated extracellular volume in conditions such as congestive heart failure, hepatorenal syndrome or sepsis. Hypoperfusion activates the juxtaglomerular complex (renin-angiotensin-aldosterone (RAA) axis) promoting avid reabsorption of sodium and water in an attempt to replenish the intravascular volume. Nonsteroidal anti-inflammatory medications that inhibit cyclooxygenase-1 and cyclooxygenase-2 enzyme activity diminish the formation of prostaglandin vasodilators.

Upon activation of the RAA axis, the release of angiotensin causes vasoconstriction of the glomerular efferent arteriole (i.e. closing the exit “valve”) thereby increasing intracapillary pressure and improving transglomerular filtration. The administration of angiotension converting enzyme inhibitors to patients with renovascular disease is dangerous since it inhibits this compensatory mechanism, dilates the efferent arteriole and thus decreases ultrafiltration pressure.

Mechanical ventilation and conditions that increase intrathoracic pressure and reduce preload (pneumothorax, cardiac tamponade) may also lead to renal hypoperfusion and renal failure. This is particularly true during states of inadequate cardiac preload.

Renal or intrinsic AKI (acute tubular/interstitial injury)

Parenchymal damage prevents the kidney from absorbing water and electrolytes and prevents the elimination of the byproducts of catabolism (creatinine and urea). Tubular casts precipitate secondary to urinary stasis, low pH and increased urinary concentration, thereby “plugging” the fine tubular system. This causes acute tubular obstruction, leaking of fluid into the interstitium, loss of epithelial integrity and epithelial damage. This phenomenon is known as acute tubular necrosis (ATN). For example, myoglobin can cause direct injury to the renal epithelium through exposure to free oxygen radicals that originate from the oxidation of ferrous oxide to ferric oxide [16].

Acute interstitial nephritis (AIN), an inflammatory infiltration of the extraglomerular structures (tubules and interstitium), leads to acute epithelial injury and renal dysfunction due to the activation of proinflammatorycytokines. This process is usually secondary to the use of medications (e.g. aminoglycosides, amphotericin). AIN is usually self-limited and rarely progresses to permanent renal injury.

Radiocontrast dyes subject the renal tubular system to high solute loads. This imposes high energy demands to the renal medulla resulting in increased tubular activity. This significantly increased metabolic demand easily leads to interstitial hypoxia and subsequent renal injury since the renal medulla is an area of limited blood flow. Kidney injury from contrast dye is known as contrast-induced nephropathy (CIN) [17].

Other causes of interstitial nephritis include bacterial and viral infections, systemic lupus nephritis, and acute renal transplant rejection.

PostrenalAKI (postrenal obstruction)

In postrenalAKI obstruction of the urinary outflow leads to decreased ultrafiltration pressure and acute tubular injury. The obstruction leads to the backflow” of urine causing tubular hypertension. Obstruction lasting more that a few days leads to hydronephrosis or dilatation of the collecting system.

Common causes of postrenalAKI include papillary necrosis, posterior urethral valves, urethral strictures and acute neurogenic bladder which is observed in trauma or the presence of a pelvic mass.

Multifactorial AKI (sepsis)

Sepsis-related AKI accounts for one-third of cases of renal injury in children. Injury mechanisms include systemic hypoperfusion, the release of proinflammatory mediators, decreases in anti-inflammatory mediators and the activation of the coagulation cascade leading to intrarenal microthrombosis. Recent evidence has demonstrated that upregulation of metalloproteinase-8 and elastase-2e may play a role in sepsis-related AKI. Whether these biomarkers are causative of AKI or simply a consequence of an increased proinflammatory state is unknown.

Staging

The Acute Dialysis Quality Initiative (ADQI) Group, a multidisciplinary group working on developing evidence-based guidelines for the treatment of acute kidney injury (AKI), identified specific characteristics of AKI to help define and measure outcomes. [18].

According to ADQI guidelines, the acute deterioration of kidney function follows a series of stages to finally reach a complete and permanent cessation of renal function. These are known as the RIFLE criteria for acute renal dysfunction and are characterized by a progressive decline of UO and GFR and increasing plasma creatinine.

R= Risk of renal dysfunction

I= Injury to the kidney

F= Failure of kidney function

L= Loss of kidney function. Indicates persistent loss requiring renal replacement therapy (RRT) for more than 4 weeks

E= End stage kidney disease. Indicates need for RRT for more than 3 months.

The correlation between the RIFLE criteria and outcomes from renal failure has been investigated in depth. The initiation of renal replacement therapy (RRT) in early stages or less severe renal failure (RIFLE-R and I) was associated with improved outcomes and decreased thirty day mortality. In contrast, when RRT was initiated in the setting of more severe stages (RIFLE-F and L), the thirty day mortality approached almost 50% [19].

A pediatric version of the RIFLE criteria was developed in 2007. The pediatric RIFLE (pRIFLE) differs from the adult criteria as it considers only UO and GFR but not serum creatinine. Unfortunately, a recent review demonstrated that the pRIFLE criteria were inconsistent when used to determine the morbidity and mortality outcomes in children with renal failure [20].

Most recently, the Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI) Work Group delineated an international guideline to help define and stage AKI in adults and children based on changes in serum creatinine and urine output [21].

Chronic kidney disease is defined as the persistence of renal dysfunction beyond the period of resolution of the causative injury and is associated with a progressive decline in the glomerular filtration rate (GFR).

End stage kidney disease refers to chronic kidney disease requiring dialysis or kidney transplant.

hemo- vs peritoneal dialysis

from the Practicing Surgeons Curriculum (Pamela Scalise and Alex Cuenca)

Presentation and Assessment

How does dehydration present in children?

Children can present with various signs and symptoms of dehydration which include the following:

• history of vomiting and/or diarrhea
• low urine output
• fever
• weight decrease
• increased capillary refill time (greater than two seconds)
• dryness of lips and mucous membranes, lack of tears
• sunken fontanel
• mental status changes
• heart rate increase usually without changes in blood pressure

It is critical to obtain a history regarding the type and volume of the child’s intake as well. A physical exam may be very helpful in estimating fluid deficit. Dry mucous membranes, increased thirst and mildly diminished urine output may indicate a 30-50 ml/kg deficit in infants and adolescents. Tachycardia associated with very low or no urine output, sunken eyes, sunken fontanels and loss of skin turgor may indicate a 60-100 ml/kg deficit. Severe deficits (90-150 ml/kg) can be marked by absence of tears, delayed capillary refill, hypotension, mottled skin and potential neurological changes [22].

What are the symptoms of hyper- and hyponatremia and how do you evaluate patients with these electrolyte abnormalities?

• serum blood urea nitrogen, creatinine and urinalysis to assess renal function
• other electrolytes (including HCO₃₎

Hyponatremia

Hyponatremia is defined as a serum sodium less than 128 mEq/L in the early newborn period and less than 135 mEq/L in children. In the early newborn period, hyponatremia can occur from increased maternal free water intake or the syndrome of inappropriate antidiuretic hormone (SIADH) associated with conditions such as pneumonia, meningitis or intraventricular hemorrhage. When hyponatremia is observed, one should make sure that it is not due to factitious circumstances such as is seen with hyperglycemia, hypertriglyceridemia or increased serum immunoglobulins (e.g multiple myeloma). In the later newborn period and in older children, hyponatremia is frequently seen in a variety of volume states [23].

Hypovolemic hyponatremia is usually observed with significant gastrointestinal losses in conjunction with an appropriate ADH secretory response. It is also seen with diuretic use (e.g. thiazide), skin losses, intense exercise and renal salt wasting. Renal salt wasting is seen with conditions such as cerebral salt wasting after intracranial surgery, meningoencephalitis, and head trauma. Renal salt wasting can also be seen with primary tubular disorders associated with adrenal insufficiency.

Normovolemic hyponatremia occurs when there is inappropriate secretion of ADH. This can occur secondary to systemic causes (pulmonary, central nervous system and endocrine disorders) and medications. Normovolemic hyponatremia can also be seen with primary polydipsia without excess ADH secretion [23].

Hypervolemic hyponatremia is usually seen with conditions that lead to an increase in effective blood volume such as occurs with nephrotic syndrome, cirrhosis and congestive heart failure. Renal failure can also increase the total extracellular volume despite normal ADH secretion.

The clinical manifestations of hyponatremia depend on the duration and severity of the hyponatremia. Acute drops in sodium are less well tolerated than chronic hyponatremia since they cause rapid osmotic shifts leading to cerebral edema and neurological symptoms. Significant symptoms usually occur with a serum sodium less than 125 mEq/L and include headache, lethargy and seizures. The neurological symptoms observed with chronic hyponatremia may be milder and include restlessness, weakness, irritability and fatigue.

Hypernatremia

Hypernatremia, defined as a serum sodium greater than 150 mEq/L, usually occurs as a result of free water loss. In the newborn period, inadequate feeding can raise sodium concentrations. In the older child, the loss of free water in the urine or gastrointestinal tract can also cause hypernatremia. An impaired ability to concentrate urine due to a deficiency in ADH or resistance to its effects can lead to the production of dilute urine and a subsequent increase in the serum sodium concentration. This is termed diabetes insipidus (DI) and can either be central (reduced production) or nephrogenic (renal resistance) in origin. Medications such as lithium, amphotericin, ifosfamide and cidofovir can also lead to nephrogenic DI. Very occasionally, iatrogenic administration of hypertonic or isotonic solutions (to replace hypotonic loss), osmotic agents (e.g. mannitol) or excessive sodium intake can lead to hypernatremia [24].

The clinical manifestations of hypernatremia are dependent on the acuity of the disease. As most cases of hypernatremia are secondary to fluid losses, general symptoms include tachycardia, low blood pressure and reduced peripheral perfusion. The initial manifestations of acute hypernatremia include irritability, restlessness, weakness, vomiting, muscular twitching, fever and, in infants, a high pitched cry and tachypnea. With serum sodium levels above 160 mEq/L, altered mental status can progress to coma and seizures. Very rapid rises in serum sodium can lead to vascular injury and subarachnoid hemorrhage. With chronic hypernatremia, the symptoms are usually less severe and nonspecific. Cerebral adaption to chronic hypernatremia includes the movement of fluid from the cerebrospinal fluid as well increased intracellular osmotic molecules that promote further fluid uptake into neuronal cells. This adaptation prevents significant symptoms but can lead to cerebral edema if correction of the hypernatremia with free fluid replacement occurs too rapidly [25].

Patients with sodium abnormalities should be assessed with

• plasma osmolality
• urine osmolality
• urine sodium and fractional excretion of sodium (FENa)
• serum glucose and triglyceride levels to evaluate for factitious hyponatremia

(see Medical Treatment)

What are the symptoms of hyper- and hypokalemia and how do you evaluate patients with these electrolyte abnormalities?

Hypokalemia

Hypokalemia is defined as a serum potassium of less than 3.5 mEq/L with symptoms usually occurring when levels drop below 3.0 mEq/L. The causes of hypokalemia include gastrointestinal or urinary losses and intracellular shifts. Excess free water intake can also lead to hypokalemia.

Gastrointestinal losses are the most common cause, especially diarrhea, due to the high content of potassium in liquid feces. Upper gastrointestinal losses result in hypokalemia only after the onset of metabolic acidosis. H⁺ ions shift from the intracellular space to the extracellular space. Potassium then moves to the intracellular space to maintain electroneutrality. In addition, hypovolemia increases aldosterone levels which further enhances the urinary loss of potassium.

Other causes of urinary potassium loss include genetic tubular injury, genetic tubular disorders (Bartter and Gitelman syndrome), renal tubular acidosis (RTA type 1), diuretic therapy, osmotic diuresis and amphotericin B nephrotoxicity.

Insulin activates the Na-K ATPase pump forcing K⁺ into the intracellular space and thus conditions associated with increased insulin activity can also lead to hypokalemia. Beta adrenergic agents act in a similar fashion.

The clinical manifestations of hypokalemia are rare with potassium levels greater than 3.0 mEq/L unless there is a rapid drop. Muscle weakness can progress from the lower extremities to the trunk followed by the upper extremities ultimately leading to paralysis and respiratory failure. Smooth muscle is also affected and can result in an ileus. Other muscle symptoms include cramps, fasciculations and rhabdomyolysis.

Hypokalemia can also result in cardiac arrhythmia such as premature atrial and ventricular beats, atrial, junctional or ventricular tachycardia, atrioventricular blocks, and fibrillation. The electrocardiogram can show PR prolongation, T wave flattening and ST depression. U waves are also seen as hypokalemia worsens.

Hyperkalemia

Hyperkalemia is defined as a serum potassium greater than 5.5 mEq/L. It can result from excessive intake (iatrogenic or otherwise), blood transfusions or cellular injury as observed in exercise, rhabdomyolysis, tumor lysis syndrome and hemolytic processes. In addition, metabolic acidosis leads to an intracellular shift of H⁺ ions leading to extracellular shift of potassium.

Renal failure leads to hyperkalemia as a result of decreased glomerular filtration and tubular dysfunction. Immature tubular function in premature newborns results in a higher baseline plasma potassium levels. Furthermore, pyelonephritis and sickle cell renal tubular injury reduces the response to aldosterone that can also lead to hyperkalemia.

Impaired arterial blood volume can reduce tissue perfusion leading to metabolic acidosis and hyperkalemia. Other rarer causes of hyperkalemia include congenital adrenal hyperplasia, adrenal insufficiency, pseudohypoaldosteronism and certain medications including potassium-sparing diuretics such as spironolactone and angiotensin converting enzyme inhibitors.

Pseudohyperkalemia is seen in hemolyzed samples and in children with marked leukocytosis and thrombocytosis.

Although electrocardiographic changes may be seen, the clinical manifestations of hyperkalemia are rare if the serum potassium is less than 7 mEq/L, . As levels rise, muscle weakness or paralysis may occur as well cardiac conduction abnormalities. With milder hyperkalemia tall, peaked T waves and shortening of the QT interval occurs. As hyperkalemia worsens, peaked T waves are associated with a prolonged PR interval, diminished P waves and a wide QRS complex and increased R wave. With serum potassium levels above 8 mEq/L bundle branch block, ventricular fibrillation and asystole can occur. In fact, hyperkalemia should be considered in the setting of cardiac arrest of unknown etiology in a child.

Patients with potassium abnormalities should be assessed with:

• complete blood count, platelets and serum lactic dehydrogenase to assess for blood disorders
• serum creatine kinase to identify muscle injury
• serum aldosterone and plasma renin activity in patients for whom there is clinical suspicion for underlying endocrinopathy.
• urine potassium levels
  • random levels should be less than 15 mEq/L in hypokalemia. Higher values suggest renal potassium losses.
  • random levels should be greater than 40 mEq in hyperkalemia. Lower levels suggest renal origins.
• urine sodium levels – low random urinary sodium values (less than 20 mEq/L) suggests active sodium reabsorption thus making less sodium available for exchange with potassium in the distal tubule.

(see Medical Treatment)

What are the symptoms and causes of hyper- and hypocalcemia?

Hypocalcemia

Hypocalcemia is defined as an ionized calcium concentration less than 0.9 mmol/L. Low serum albumin can lead to falsely depressed levels. True hypocalcemia is seen with DiGeorge syndrome, hyperphosphatemia, hypoparathyroidism, magnesium deficiency, renal failure and diuretic therapy. In children born to mothers with maternal hyperparathyroidism, transient neonatal hypoparathyroidism can result in hypocalcemia.

Clinical manifestations of hypocalcemia include jitteriness, irritability, seizures, stridor and possibly tetany that includes carpopedal spasm. Prolonged QT interval and a flattened T wave may be observed on ECG. Myocardial contraction can be reduced resulting in diminished cardiac output.

Hypercalcemia

Hypercalcemia, which is very uncommon in newborns, is defined as a total serum calcium concentration greater than 12 mg/dL or an ionized calcium level greater than 1.5 mEq/L. It is seen with hypophosphatemia, hyperparathyroidism, Vitamin D poisoning, adrenal insufficiency and diuretic therapy.

Clinical manifestations include gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Peptic ulcers and pancreatitis are observed in patients with hyperparathyroidism but are not related to hypercalcemia. Similarly, the bone resorption that can occur with secondary hyperparathyroidism is associated with hypercalcemia but is not caused by hypercalcemia. Renal dysfunction can lead to polyuria, nocturia, polydipsia, nephrolithiasis and sometimes renal failure. Psychological and emotional symptoms occur with levels greater than 12 mg/dl and include confusion, delirium, emotional changes, polyhypotonia, vomiting, encephalopathy and possibly coma. These symptoms have sometimes been referred to as "moans, stones, groans, bones and psychiatric overtones." Severe hypercalcemia can cause arrythmias, shock, renal failure and death.[26]

What are the symptoms and causes of hypo- and hypermagnesemia?

Hypomagnesemia is unusual and is often associated with persistent hypocalcemia and hypokalemia. Clinical signs and symptoms are often reflective of associated electrolyte abnormalities. These include anorexia, weakness, lethargy, tremor, tetany, seizures (especially in children), and arrhythmias. Hypomagnesemia can lead to long QT syndrome and "torsades de pointes," especially in conjunction with hypokalemia, which results in ventricular fibrillation.[27]

Hypermagnesemia, defined as a serum magnesium concentration greater than 3 mg/dL, usually occurs secondary to maternal magnesium therapy for pre-eclampsia or as a tocolytic to stop preterm labor. Neonatal symptoms include hypotonia, hyporeflexia, hypotension, apnea and vasodilatation with marked flushing.
 The treatment is usually supportive until the magnesium level gradually falls secondary to renal excretion. With severe cases the administration of intravenous calcium may be of benefit. Infants with severe hypermagnesemia may require assisted ventilation and blood pressure support.

(see Medical Treatment)

Medical Treatment

Maintenance fluid requirements are calculated based on the lean body weight or body surface area. Several issues can affect the suggested maintenance rate of fluid administration including environment, patient- and disease-related factors.

What are the normal fluid maintenance requirements of premature and term infants?

The initial normal fluid requirements in premature and term infants can vary as they offload fluid.

Neonatal fluid requirements can change quickly in critical illness, thus frequent adjustments in fluid management are often necessary. The most accurate way to assess fluid status is by monitoring urine output and aiming for 1 to 2 mL/kg/hr while using the above guide as a starting range.

For infants that are greater then 32 weeks gestational age, more than one week in age, and greater than 1.5 kg, daily fluid requirements can be calculated using the Holliday and Segar formula at 4 mL/kg/hr [1].

During the first week of life, infants are expected to lose 10-15% of their body weight. Premature infants will lose even more. Environmental factors that impact the amount of fluids needed may include ambient temperature and increased humidity.

What are the normal fluid maintenance requirements of children and adolescents?

The Holliday and Segar approach was deduced from the daily caloric expenditure of 100 kcal/kg for infants from three to ten kilograms, adding 50 kcal/kg for infants weighing from ten to twenty kilograms, and 20 kcal/kg for every kilogram above 20 kg. Since one kcal requires one mL of water for metabolism, this resulted in 1000 mL/day for a 10 kg child, 1500 mL/day for a 20 kg child and 1700 mL/day for a 30 kg child. This was further simplified into the "4:2:1 rule" which provided an hourly rate of 4 mL/kg up to 10kg, another 2 mL/kg for every kg above 10kg and 1 mL/kg for every additional kg above 20kg. Thus, the normal fluid requirement of a child that weighs between 11 to 20 kg is 1000 mL plus 50 mL/kg per 24 hours for each kilogram between 11 to 20 kg. For children over 20 kg, the volume is 1500 mL plus 20 mL/kg per 24 hours for each kilogram between 21 kg and 70 kg. It is important to note that this formula only addresses maintenance fluid losses and does not account for any additional deficit or concurrent fluid loss (e.g. nasogastric drainage) [1].

What are the normal electrolyte requirements of infants, children and adolescents?

Magnesium

In general, magnesium should not be added to the parenteral nutrition of infants whose mothers have received a therapeutic dose of magnesium (i.e. for tocolysis or prophylaxis against eclampsia). The serum magnesium levels should be checked first and magnesium added if serum magnesium is not elevated.

How are abnormal levels of sodium, potassium, calcium and magnesium managed?

Hyponatremia is usually due to an excess of free water (usually iatrogenic) rather than too little sodium. Limiting the amount of hypotonic volume resuscitation may improve the deficit. The sodium deficit calculation is

[(normal Na(mEq/L)) - measured Na(mEq/L)] x TBW(L)

A normal serum sodium is 135 mEq/L and the TBW can be estimated as 0.6 L/Kg x body weight in kilograms.

If the hyponatremia is symptomatic (e.g. seizures) and serum concentrations are less than 120mEq/L, giving 5 mL/kg of 3% saline generally increases the serum sodium by 3 to 5 mEq/L and can be repeated until the seizures stop. Depending on the duration of hyponatremia (i.e. acute or chronic), ongoing replacement is then determined. The rate of sodium rise should be no more than 0.5 mEq/L/hr to prevent central pontine myelinolysis. Central pontine myelinolysis is a noninflammatory demyelination that usually occurs within the central basis pontis, though at least in 10% of the demyelination also occurs in extrapontine regions, including the mid-brain, thalamus, basal nuclei, and cerebellum. The exact mechanism that strips the myelin sheath is unknown. Sodium deficits are usually corrected over a 24 to 48 hour period to prevent central pontine myelinolysis.

Hypernatremia is defined as a serum sodium greater than 150 mEq/L. Since hypernatremia usually results from a free water deficit, the correction is first calculated by determining the free water deficit.

Free Water Deficit = total body water x weight (kg) x (current Na/desired Na - 1))

(Using 145 mEq/L as the desired sodium and estimating the TBW as 0.6 L/kg x body weight in kg).

If the hypernatremia is severe (i.e. greater than 160mEq/L), the rate of correction should not exceed 1 mEq per hour or 15 mEq per day because the patient may suffer seizures due to over aggressive correction[30]. In extreme cases of hypernatremia, dialysis may be needed to correct the severe volume overload and hypernatremia.

Hypokalemia in the acute setting is best managed parenterally with a potassium dose of 0.3 mEq/kg/hr or 40 mEq (total)/hr, whichever is less. For parenteral replacement, the maximum given through a peripheral intravenous line is 40 mEq/L. Larger amounts (i.e. a "K-run" of 0.5-1 mEq/kg) should be given through a central venous catheter over 3 hours with appropriate monitoring, most commonly in an intensive care setting. If hypokalemia can be managed orally, 2 to 4 mEq/kg/day can be given enterally. Hypokalemia can be difficult to correct if there are concurrent magnesium and chloride deficiencies.

Once hyperkalemia is diagnosed, the patient should be placed on cardiac monitoring and an electrocardiogram (ECG) obtained. Of course, all sources of potassium should be discontinued [31]. If mild (serum potassium less than 7mEq/L and the ECG is normal) then sodium polystyrene sulfonate (Kayexalate®) can be started at 1 gm/kg/dose either orally or per rectum (PR). If given PR it must be retained for at least 20-30 minutes to be effective. The dose can be repeated every 4-6 hours. Each gram per kilogram dose will decrease the serum potassium level by 1 mEq/L. Importantly, sodium polystyrene sulfonate can impose a sodium load so it should be used cautiously in cases of oliguric renal failure or cardiac disease.

1. Sodium polystyrene sulfonate should be started.
2. Intravenous (IV) calcium gluconate (100 mg/kg) should be given over 5-10 minutes as a first maneuver to provide myocardial cell stabilization. Since the effect is often short lived, the dose can be repeated after five minutes if the ECG changes persist or recur. If the serum phosphorus is elevated, calcium should be used cautiously because CaPO₄ precipitation can occur.
3. Sodium bicarbonate can be given at 1-2 mEq/kg IV over 5-10 minutes. One should be cautious if the patient’s calcium is low because raising the pH decreases serum calcium levels and aggravates membrane instability. Sodium bicarbonate can also be repeated every 15-30 minutes.
4. The administration of glucose and insulin can also shift the potassium to the intracellular space. In nondiabetics, 0.5 to 1 gm/kg of glucose is given IV over one to two hours and increases endogenous insulin secretion. This usually lowers plasma potassium 1 to 2 mEq/L within one hour. In diabetics or patients with insulin resistance and hyperglycemia, the insulin alone may be sufficient. In some cases, a glucose/insulin drip may be necessary (0.5 to 1 gm/kg glucose with 0.3 U regular insulin per gram glucose over 2 hours). In such cases, the serum glucose should be monitored every 10-15 minutes. Loop diuretics can also be considered if the kidney function is normal. For severe, unrelenting hyperkalemia prepare for dialysis.

Beta-adrenergic agonists can also be quite effective in hyperkalemia but are perhaps somewhat more controversial secondary to the need for assistance from respiratory therapy and more likely to produce side effects. In the United States, the most commonly used preparation is nebulized albuterol. The dose for treating hyperkalemia, 10 mg, is substantially higher than the usual dose for the treatment of bronchospasm. The peak hypokalemic effect occurs at 90 minutes.

The patient with hypocalcemia should be placed on an ECG monitor as arrythmias or cardiac arrest can occur during calcium replacement. Severe hypocalcemia can also lead to seizures. For parenteral replacement, 10% calcium gluconate (which equals 100 mg/mL calcium gluconate or 9 mg elemental calcium/100 mg calcium gluconate) or 10% calcium chloride (which equals 100 mg/mL CaCl₂ or 27 mg elemental calcium/100 mg calcium chloride) can be given. Typically, 1 mL/kg of 10% calcium gluconate is administered. Otherwise, calcium may be replaced in doses of 200 to 500 mg/kg/day. Oral replacement with calcium supplements and vitamin D may be used in more chronic situations.

The most common cause of hypercalcemia in admitted patients is hypophosphatemia. Hence, serum phosphate should be checked and corrected first. Next, hypercalcemia should be treated by eliminating possible causes such as thiazide diuretics and hypervitaminosis of vitamins D and/or A. Increasing urinary excretion of calcium by increasing fluid intake with 20 mL/kg fluid boluses (with or without furosemide) may also be considered. Intestinal absorption of calcium can be decreased by increasing dietary phosphate and/or providing glucocorticoids. Bone resorption can be decreased by giving calcitonin or bisphosphonates. Dialysis should also be considered if the hypercalcemia is severe.

If possible, the first line treatment for hypomagnesemia should be oral supplementation in order to decrease the rate of hypotension that can be associated with intravenous replacement. However, oral replacement may be associated with diarrhea. The usual dose is 6 to 15 mg/day of elemental magnesium divided into four doses per day. Parenteral replacement is 0.2 to 0.4 mEq/kg/dose every occurs slowly over 4-6 hours if the patient is symptomatic.

Hypermagnesemia is best treated with calcium administration provided at the same doses as the treatment of hypocalcemia. If the symptoms are severe, loop diuretics with saline administration may also be useful.

Medical Decision Making

Intravenous fluid choices should be tailored to the age of the patient and the clinical situation. Determining the fractional excretion of sodium can help to determine the cause of decreased urine output.

What options are available for fluid administration?

Options for intravenous fluid choices include

What is the recommended type of intravenous fluid for use in neonates, children and adolescents?

The recommended initial intravenous fluid for neonates greater than 1500 g and full term infants is 10% dextrose in water (D₁₀W). On days two through seven, sodium and potassium are added. After day seven, D₅ to D₁₀ with one-quarter normal saline is started if the infant has not yet been placed on parenteral nutrition. The glucose infusion rate (GIR) is closely measured and starts at 4 to 6 mg/kg/min. Infants less than 1500 g are started on D₁₀W, with sodium and potassium added through days two through seven.

Children (i.e. greater than two months of age) and adolescents who require fluid resuscitation should initially receive either normal saline or lactated Ringers. Normal saline, with dextrose if desired, or lactated ringers can then be started for maintenance fluid utilizing the Holliday-Segar method of the 4-2-1 rule [1].

isotonic maintenance fluids

Infographic from the APSA Practicing Surgeons’ curriculum (Pramod Puligandla)

Should hypotonic or isotonic fluids be administered to patients requiring intravenous fluids?

A Cochrane Review has demonstrated that hypotonic fluid should not usually be given to children outside of the neonatal period as it may result in unrecognized hyponatremia and morbidity. Isotonic fluid should always be the choice of fluid for children and adolescents [32][33].

video link Isotonic maintenance fluid

When and how should hypertonic saline be used?

Hypertonic (three percent) saline has been shown to be effective in the management of burns , seizures due to severe hyponatremia and elevated intracranial pressure. In two separate studies of children with traumatic brain injury (TBI), hypertonic saline was shown to increase cerebral perfusion pressure in the three days after head trauma when compared to lactated Ringers solution [34][35]. It is difficult to make recommendations on giving hypertonic saline in the setting of TBI since one study gave the hypertonic saline over three days as the fluid of choice and the other study gave it as a one-time bolus following resuscitation. A 5 mL/kg bolus of 3% saline will usually increase serum sodium levels by 3 to 5 mEq/L. It can be given either via peripheral or central intravenous access.

What are the considerations in the diagnosis and fluid management of the patient with low urine output?

The first step in the management of a patient with low urine output is to assess whether the cause is prerenal, renal or postrenal. A history and physical exam are important to determining the cause of the low urine output. The initial laboratory investigations should include the measurement of the serum electrolytes, urea and creatinine with a urinalysis. A prerenal cause implies poor perfusion of the kidney secondary to hypovolemia; a renal cause implies intrinsic renal disease or damage; a postrenal cause implies an obstruction to urine excretion. Prerenal causes are the most common causes of low urine output (up to 70% of cases). Extracellular fluid losses from gastroenteritis, burns, hemorrhage and excessive diuresis are the most common examples. Prerenal azotemia is usually associated with blood urea nitrogen to creatinine ratios that are greater then twenty. In cases of intrinsic causes of renal failure, the ratio is usually ten. Another way to distinguish between prerenal and renal etiologies is to calculate the fractional excretion of sodium (FENa).

fractional excretion of sodium

The FENa is usually less than one percent in adults and children and less than 2.5% in infants with prerenal causes of acute kidney injury. If the FENa is greater than two to three percent in adults and children then the oliguria is usually secondary to intrinsic renal etiologies of renal insufficiency. Diuretics administered in the 24 hours prior to determining the FENa can confound the results. When indicated, postrenal causes of oliguria can be evaluated using renal ultrasound, voiding cystourethrography, nuclear renal flow scanning and computerized tomography of the abdomen.

Fluid management can be initiated once the underlying reason for oliguria has been determined. Prerenal causes indicate that the patient should be resuscitated with 20 to 40 mL/kg of normal saline or lactated Ringers solution over thirty to sixty minutes. The preservation of urine output, even with diuretics, has not been shown to influence renal recovery, the need for dialysis or survival in patients with acute renal failure [36]. Furthermore, low dose dopamine has not been shown to prevent renal failure, decrease the need for dialysis or effect mortality [37].

How should perioperative fluids be managed in patients with renal failure?

The optimal way to manage anesthesia in pediatric renal failure patients has not been well studied. One adult anesthetic guideline suggests that intravenous fluids should be limited since volume overload in dialysis patients is associated with increased cardiovascular morbidity and mortality [38]. For minor procedures, intravenous fluids should be limited to less than 1 mL/kg. Sodium levels should be closely monitored as renal failure patients may be prone to hyponatremia. Hyperkalemia is not usually treated unless the potassium is >6 mEq/L. Calcium and phosphorus levels also should be closely monitored [39].

Preoperative Preparation

When should patients be made NPO prior to a procedure and what fluids should be administered preoperatively?

The recommended fasting guidelines, based on the European Society of Anaesthesia (2011) suggest [40]

• two hours for clear liquids
• four hours for breast milk
• six hours for non-human milk or infant formula
• eight hours for solid food

These guidelines were also supported by a Cochrane review from 2009 [41].

In general, preoperative intravenous fluid is seldom necessary with these revised NPO guidelines. Special consideration is needed for patients with metabolic diseases, mitochondrial dieasaes, insulin-dependent diabetes or sickle cell disease. These children should be scheduled as early in the day as possible to minimize their NPO time. All of these conditions require communication between the anesthesiologist, surgeon and medical sub-specialist caring for the child. In general, patients with metabolic diseases may need to have a modified NPO time or early admission to the hospital to begin a dextrose containing solution at the time they are made NPO. There may also be certain medications that must be avoided with regards to their specific disease. Children with mitochondrial diseases need to avoid ketoacidosis and may also need a modified NPO time or admission to begin a dextrose containing solution when they are made NPO. Lactated ringers should also be avoided since it could worsen any existing ketoacidosis. For insulin-dependant diabetics, oral agents and long-acting insulin are usually discontinued before surgery, although some of the longer acting agents maybe appropriate for basal coverage. Sliding scale subcutaneous insulin for perioperative glycemic control may be a less preferable method because it can have unreliable absorption and lead to erratic blood glucose levels. Intravenous insulin infusions have a more predictable absorption rate. Importantly, one can rapidly titrate insulin delivery to maintain proper glycemic control. Insulin is typically infused at 1 to 2 U per hour and adjusted according to the results of frequent blood glucose checks. A separate infusion of dextrose can prevent hypoglycemia [42]. Patients with sickle cell disease also need to avoid dehydration and often need pre-operative hydration [43].

How much and what type of intravneous fluid should be given in the operating room?

Initial maintenance intravenous fluids in the operating room should include normal saline or lactated Ringers solution. Neonates less than 48 hours of age require supplemental dextrose. Replenishment of third space fluid losses is an important consideration. For cases anticipating minimal surgical losses (e.g. hernia operation), the rate of fluid replacement should 1 to 2 mL/kg/hr. For anticipated moderate fluid losses (e.g. cholecystectomy) the rate of replacement should be 4 to 7 mL/kg/hr. For larger losses (e.g. elective bowel resection), a replacement rate of 6 to 10 mL/kg/hr is appropriate. For major abdominal operations losses of 15 to 20 mL/kg/hr may need to be replaced. Indeed, a laparotomy for necrotizing enterocolitis may require fluid replacement as high as 50 mL/kg/hr [44].

What should be done with parenteral nutrition and lipids that are running when the patient arrives in the operating room?

There is no consensus regarding the continuation of total parenteral nutrition (PN) in the operating room. Lipids solutions are generally stopped. However, neonates and children on PN are at risk of hypoglycemia if the PN is stopped abruptly, and thus intraoperative glucose monitoring is required. A study surveying the practices of pediatric anesthesiologists with respect to PN reported that 28% discontinue it and switch to another glucose containing fluid while 35% turn the rate down to half maintenance. Another 33% continue the PN at its original rate [45].

Postoperative Care

Postoperative patients should receive isotonic fluid and replacement of additional abnormal fluid losses.

What are the patient responses to an operation?

The response to surgical stress is governed by complex neuroendocrine and cytokine interactions. Initially, the onset of surgery stimulates the sympathetic nervous system and the hypothalamic-pituitary axis. In addition to causing tachycardia and hypertension, sympathetic stimulation leads to altered hepatic, pancreatic (increased glucagon, decreased insulin production) and renal function. At the same time, ACTH secretion by the anterior pituitary leads to cortisol release. Cortisol has many metabolic effects, most notably (a) glycogenolysis and reduced glucose utilization leading to hyperglycemia, (b) skeletal muscle breakdown in order to provide substrate for gluconeogenesis, and (c) lipolysis. Increased cortisol and glucagon, in combination with a relative insulin "resistance" due to α₂ adrenergic effects, accelerates lipid breakdown to fatty acids and glycerol. Fatty acids are subsequently oxidized to acyl CoA to produce ketone bodies that serve as an important alternative fuel source, while glycerol can be used in gluconeogenesis. Cortisol may also be implicated in down-regulating the inflammatory response by decreasing the production of inflammatory mediators such as cytokines and leukotrienes.

Anesthesia and surgery also lead to sodium and water retention that is proportional to the length of the operation. Hypovolemia is a major trigger for these effects but retention can occur even in its absence. Decreased renal blood flow affects the renin-angiotensin-aldosterone (RAS) system which ultimately leads to the resorption of sodium and water, and the excretion of potassium. Antidiuretic hormone or arginine vasopressin (ADH or AVP) is also released in response to surgical stress and pain, amongst other stimuli [2]. ADH leads to the insertion of aquaporins within the renal tubules that increase the resorption of free water; this acts to maintain intravascular volume and cardiovascular homeostasis. However, free water resorption can also lead to hyponatremia [46]. This effect can persist for 3-5 days after surgery. The RAS system may be further stimulated response to reduced serum osmolality, thereby increasing sodium and water retention.

In addition to these neuroendocrine effects, cytokines also play a role in the bodies response to surgical stress. Cytokines may be pro- and anti-inflammatory mediators and are important since they affect gene expression, immunocompetence and cell proliferation, lead to the production of counter regulatory hormones and facilitate cell-to-cell communication. The most important cytokines released in response to surgical stress include the pro-inflammatory TNF-α, IL-1 and IL-6, as well as the anti-inflammatory IL-1ra and IL-10.

What fluid should be used in the immediate postoperative period?

Isotonic fluids such as normal saline or Ringers lactate should be used for the first several days after surgery both for maintenance as well as any additional fluid requirements in order to decrease the risk of hyponatremia. Intravenous solutions should also include five percent dextrose until higher nutrient solutions are initiated. (see Nutrition)

When does a postoperative diuresis occur?

Postoperative diuresis generally occurs after three to four days as ADH levels begin to decrease. Should this not occur, concerns about pain control and infection should be raised as possible causes for prolonged ADH secretion. Some medications, such as narcotics, can also produce excess ADH secretion in the absence of hypovolemia [2].

How are abnormal fluid losses replaced?

Abnormal ongoing fluid losses, especially those from the gastrointestinal tract, require replacement both for quantity and content. The electrolyte content of gastrointestinal fluids varies depending on the area of intestine involved. The treatment of gastric fluid losses begins with half normal saline with 20 mEq/L of KCl whereas biliary and intestinal losses are replaced with lactated Ringers solution. Measurement of electrolytes from lost fluids is helpful in deciding appropriate replacement. Urine output should be monitored to ensure adequate renal perfusion.

What special circumstances require individualized fluid management?

Patients with open abdominal wounds, gastroschisis,and burns have markedly elevated unmeasured losses and are addressed in those topics.

Complications

What causes iatrogenic hyponatremia and how is it managed?

Iatrogenic hyponatremia results when fluid losses are replaced with hypotonic intravenous fluids. Furthermore, elevated ADH secretion in response to operative stress or trauma leads to the retention of free water further increasing the risk for the development of symptomatic hyponatremia. Based on emerging evidence identifying this risk, postoperative patients should receive isotonic fluids for several days after surgery to minimize the development of hyponatremia and manage the condition when it is established.

video link Fluid overload from the Critical Care session during the APSA 2020 virtual meeting

Perspectives and Commentary

To submit comments about this topic please contact the editors at think@apsapedsurg.org.

Additional Resources

APSA Standardized Toolbox of Education for Pediatric Surgery (STEPS) Fluids and Electrolytes

APSA Handbook of Pediatric Surgical Critical Care

APSA Critical Care Syllabus

Discussion Questions and Cases

To submit interesting cases which display thoughtful patient management please contact the editors at think@apsapedsurg.org.

A critically ill five day old 32 week old infant weighing 2000 g has perforated necrotizing enterocolitis. The infant is getting parenteral nutrition at 120 mL/kg/day. Since the perforation was diagnosed, the neonatologist has added lactated Ringers at another 40 mL/kg/day raising the fluid input to 160 ml/kg/day. The urine output measures 0.5 ml/kg/hr.

What would be helpful to determine this patient’s fluid status?

A hematocrit, BUN, creatinine, urine sodium concentration, urine creatinine level and serum osmolality would be helpful to obtain. Calculation of the FENa will help help determine if the reduced urine output is prerenal or renal in nature.

The FENa is two percent and an elevated BUN/Cr ratio is also noted. The hematocrit is normal.

What would your next in management be?

The next step would be to administer a fluid bolus. A FENa of less than 2.5% still indicates prerenal causes in premature infants. Normal saline or lactated Ringers should be used at 10 to 20 ml/kg over thirty minutes. If the urine output does not increase, another fluid bolus is indicated. The fluid requirements for infants with necrotizing enterocolitis can increase up to 50 mL/kg/hr secondary to capillary leakage and third spacing.

References