Approach
Regardless of etiology, initial treatment should be directed at restoring sufficient intravascular volume to provide for adequate organ perfusion. Successful restoration of intravascular volume promotes hemodynamic stability, and enables identification and treatment of the underlying cause. Inadequate restoration of intravascular fluid volume can result in end-organ damage, multisystem organ failure, and death. Although there is continuity between mild to moderate and severe volume depletion, it is pragmatic to artificially divide patients into one of these two groups to determine management. Most pediatric volume depletion is caused by vomiting and diarrhea from gastroenteritis. In these cases, treatment should be aimed at decreasing nausea and vomiting to prevent severe dehydration and unnecessary hospital visits.
Commonly used indicators to determine level of volume depletion
The following indicators may be used as a guide for assessment of degree of volume depletion resulting from all causes of volume depletion discussed in the following sections.
Mild to moderate volume depletion
Preserved normal mental status
Hemodynamic stability
Mildly altered vital signs (e.g., minor degree of tachycardia)
Severe volume depletion
Altered mental status
Hemodynamic instability
Enteric losses: mild to moderate volume depletion
Enteric losses are most commonly due to acute gastroenteritis. Enteral replacement of fluid volume deficit and ongoing losses is appropriate for patients with mild or moderate dehydration.[27] Commercially prepared oral rehydration solutions (ORS) are appropriate. The WHO recommends a hypotonic ORS:
Containing 75 mEq/L sodium
Containing 75 mmol/L glucose
Having a total osmolarity of 245 mOsm/L
Commercially available ORS have a formulation close to that of the WHO-recommended ORS. A meta-analysis compared the efficacy and safety of relatively hyperosmolar ORS (≥310 mOsm/L) with the standard formulation (≤270 mOsm/L) for the treatment of adults and children with dehydration secondary to cholera, a severe secretory diarrheal illness associated with significant electrolyte loss.[28] Biochemical hyponatremia was more common in patients treated with the standard formulation but there was no difference observed in other outcomes, and analyses separating children and adults revealed no obvious trends.
[ 
]
One systematic review compared low-osmolarity ORS to a solution designed for dehydrated children who have moderate to severe nutritional wasting. No significant clinical differences were found, but it should be noted that these patients are at high risk of electrolyte derangement and fluid overload with rehydration therapies, and are particularly at risk for hypokalemia given the low potassium content of both ORS.[29] The goal of oral rehydration therapy is to replace deficits and then provide enough fluid to replenish ongoing losses. Frequent small volumes, with gradual advancement as tolerated, is preferred. A general guideline is to give 50-100 mL/kg of ORS over 2-4 hours.[13][17] Oral rehydration therapy is sometimes bypassed in favor of intravenous treatment. Clinical evidence does not support this practice unless contraindications to oral rehydration therapy exist.[12][30]
Importantly, fluids such as carbonated beverages, fruit juice, or plain water should not be used. Breastfed infants should continue nursing in addition to receiving ORS. "Gut rest" has no role in gastroenteritis. Age-appropriate diets should be instituted early in the course of gastroenteritis-associated mild or moderate volume depletion. Foods high in sugar and carbohydrates should be avoided.
Children presenting with volume depletion due to acute infectious gastroenteritis are most likely to have vomiting. This may be a significant impediment to enteral rehydration. Antiemetics are not commonly used in pediatric patients to treat vomiting related to acute gastroenteritis. However, antiemetics are occasionally used in patients who are clinically stable but are unable to take oral hydration.[31][32] Dissolvable ondansetron has been studied for use in this clinical situation in a large, randomized, controlled study.[32] Although other antiemetics are sometimes used in pediatric patients, they are generally not substantiated in the literature.
There is no defined role for the use of antidiarrheal agents in the management of pediatric volume depletion. In developing nations, early zinc supplementation has been shown to be beneficial in preventing and mitigating volume depletion associated with acute gastroenteritis.[33] There is no compelling evidence for the use of zinc supplementation in the acute management of volume depletion.
If the child is unable or unwilling to drink, nasogastric administration of ORS can be an effective alternative to the oral route, and is rapid and efficacious for children who have mild to moderate volume depletion.[34] It is even tolerated by many children with vomiting. Potential advantages of the nasogastric route include more rapid initiation of treatment, ease of nasogastric tube placement, and lower cost when compared with intravenous line placement. Potential disadvantages include risk for continued vomiting, ileus, displacement, and aspiration. Interestingly, parents are equally satisfied with nasogastric and intravenous treatments.[34] The intravenous route is preferred in conditions of hemodynamic instability secondary to volume loss, or when the volume of enteral rehydration needed to re-establish euvolemia is not tolerated by the patient during a short period of time.
Enteric losses: severe volume depletion
Severe volume depletion is a medical emergency and must be treated aggressively. Septic shock should be considered as a possible diagnosis, as it may be difficult to differentiate from severe volume depletion due to other causes or may occur concomitantly. Isotonic crystalloid solutions (e.g., normal saline or lactated Ringer's solution) are recommended for initial volume resuscitation in severe volume depletion.[22][35] Isotonic crystalloid solutions are generally readily available and inexpensive, require no special handling, and have minimal complications associated with their use. There is evidence to support the use of crystalloids over colloids for the treatment of shock, with the exception of hemorrhagic losses that may require management with massive transfusion protocols. In general, colloids have not been shown to further improve survival compared with crystalloids.
[ ]
The Food and Drug Administration (FDA) recommends that solutions containing hydroxyethyl starch (HES), an artificial colloid, should not be used unless adequate alternative treatment is unavailable.[36] HES products are associated with adverse outcomes including kidney injury and death, particularly in critically ill patients and those with sepsis.[37] In view of the serious risks posed to these patient populations, the European Medicines Agency (EMA) suspended the marketing authorizations for HES solutions in Europe in 2022.
Pediatric Surviving Sepsis Campaign guidelines recommend against the use of HES or gelatin-derived fluid in the resuscitation of children with septic shock.[22]
Colloids are also less desirable as they are considerably more expensive than crystalloids.[37][38][39] One systematic review of studies comparing the use of crystalloids and colloids for fluid resuscitation specifically in children ages 1 month to 12 years with severe infection concluded that the current evidence on fluid choice in this patient group is weak and not robust enough to make any definitive recommendations.[40] Pediatric advanced life support (PALS) guidelines recommend either isotonic crystalloids (balanced [e.g., Hartmann solution or lactated Ringer's solution] or unbalanced [e.g., normal saline]) or colloids as the initial resuscitation fluid for hypovolemic shock.[41] Based on data from adults, the pediatric Surviving Sepsis Campaign guidelines recommend using balanced/buffered crystalloid solutions, rather than normal saline or albumin for initial fluid resuscitation, due to the chloride content in normal saline increasing the likelihood of hyperchloremic metabolic acidosis when given in the large amounts often required for complete fluid resuscitation.[22] One systematic review of saline versus balanced/buffered crystalloid solutions in children with diarrhea showed shorter length of stay, higher final pH, and higher bicarbonate level in those resuscitated with balanced solution, but no differences in mortality, need for additional fluid, total amount of fluid, changes in sodium, potassium, or creatinine levels, or acute kidney injury.[42] Despite these findings, further trials of fluid resuscitation using balanced/buffered solutions in children are needed.[43]
If intravenous access cannot be obtained within the first 5 minutes, an intraosseous line should be placed. The proximal tibia and distal femur sites are frequently used. Intravenous sites in older children are the same as those for adults, but the scalp and external jugular veins are often more accessible in young infants and should be considered. Frequent reassessment of mental status, pulses, skin temperature, heart rate, BP, capillary refill, and urine output is necessary. If symptoms do not improve after 40-60 mL/kg of isotonic crystalloid (given in boluses of 10-20 mL/kg), other etiologies of the presentation (e.g., anaphylaxis, hemorrhage, intoxication, concomitant cardiovascular dysfunction) should be considered. However, children presenting in hypovolemic shock may require additional fluid replacement before shock is reversed.[5][44][45] A large-scale prospective trial of fluid resuscitation in children presenting with a severe febrile illness and impaired perfusion in resource-poor areas of Eastern Africa, found that the bolus administration of 20-40 mL of 5% albumin solution (colloid) or 0.9% saline (crystalloid) per kilogram of body weight led to increased mortality at 48 hours and at 4 weeks when compared with the no-bolus control group, although there was no increase in the incidence of pulmonary edema, elevated intracranial pressure, or neurologic sequelae.[46]
Subsequent guidance on initial fluid resuscitation from the pediatric Surviving Sepsis Campaign stratifies recommended fluid management according to whether or not the child is being treated at a center with critical care availability:[22]
If a critical care facility is present and a child has evidence of abnormal perfusion after 40-60 mL/kg of fluids (or earlier if they develop fluid overload), treatment should be escalated to include initiation of inotropes/vasopressors, which would be typically given in a critical care environment with use of advanced hemodynamic monitoring.[44]
If there is no critical care availability and the child is normotensive, maintenance fluids should be started without administration of bolus fluids. If there is no critical care availability and the child is hypotensive, up to 40 mL/kg in bolus fluid is recommended over the first hour, given as individual boluses of 10-20 mL/kg at a time and titrated according to clinical markers of cardiac output. This should be discontinued if signs of fluid overload develop.
Careful consideration of the individual circumstances of each patient and available resources should therefore be part of the assessment of the risks versus the benefits of different strategies for volume repletion.
Hemorrhagic losses
Hemorrhage is generally quite obvious as a cause of volume depletion, but the higher incidence of blunt trauma, the large size of a young child's internal organs relative to skeletal size, and the inability to communicate localized pain are all challenges to recognizing hemorrhagic losses in children. Additionally, nonaccidental trauma (physical abuse) is too often not considered early in the evaluation of a child with altered mental status or nonspecific complaints. Nonaccidental trauma frequently is associated with significant bleeding into the head, internal organs, or extremities.[8]
Volume depletion from trauma and hemorrhage should be treated initially with 20 mL/kg of isotonic crystalloid solution.[5][8] This can be repeated until signs of hemodynamic instability are improved bearing in mind the potential need for blood products/transfusion.
In addition, hemostasis is essential for correcting volume depletion. Occult bleeding is more common in children, due to patterns of traumatic injury.[8] Occult trauma should be considered in an infant or a young child presenting with altered mental status and signs of volume depletion who does not respond to crystalloid administration. A head and abdominal ultrasound or CT should be considered.
In cases of significant hemorrhagic losses when adequate oxygen delivery to vital organs is not maintained with crystalloid alone, blood products need to be repleted. Generally 5-10 mL/kg of cross-matched blood is given. In cases of active hemorrhage associated with hemodynamic instability, giving unmatched blood (trauma pack) may be necessary. Simultaneous consultation with a pediatric trauma team is indicated. Attaining hemoglobin greater than 10 mg/dL improves outcomes in children with shock.[24][47]
Coagulopathic patients with ongoing losses may require replacement of clotting factors for hemostasis. Platelets and fresh frozen plasma are given when:
Bleeding is ongoing
Blood loss is massive
The patient has received massive transfusion (50% of total blood volume).
Skin losses: exercise induced or heat stroke
Mild to moderate volume depletion:
Fluid losses through intact skin rarely cause more than mild hypovolemia. However, adolescent athletes exercising heavily in high ambient humidity and temperature can have significant losses which, if not replaced by frequent hydration with appropriate fluids, will lead to volume depletion.[16][21]
Initial management of patients with mild to moderate volume depletion is enteric replacement with ORS, as for mild to moderate enteric losses. In mild to moderate volume depletion, oral rehydration techniques should be considered as first-line therapy whenever possible. NG rehydration should be considered before attempts at intravenous resuscitation in patients with mild to moderate volume depletion who are unable to take oral fluids. Oral rehydration has been shown to be as effective as intravenous rehydration and is associated with fewer complications.[48][49] The International Liaison Committee on Resuscitation recommends the use of any readily available rehydration drink or water in the first aid setting, and suggest hydration with 4% to 9% carbohydrate-electrolyte drink as a weak recommendation.[50] In addition, environmental control is important. The patient should be moved to a neutral ambient temperature.
For patients who cannot tolerate enteral rehydration due to intractable vomiting or depressed mental status, intravenous isotonic saline is used.
In cases of skin loss from excessive sweating, the fluid lost is relatively hypotonic. After intravascular volume is restored, relatively hypotonic solutions (orally) can be used to restore total body water deficit.
Severe volume depletion:
Initial treatment is with intravenous isotonic saline 20 mL/kg, repeated as necessary to restore normal hemodynamics.
After intravascular volume is restored in cases of skin loss from excessive sweating, relatively hypotonic solutions (e.g., 0.45% normal saline) can be used to restore total body water deficit if indicated by persistent hypernatremia.
Whenever hypotonic fluids are delivered, frequent monitoring of electrolytes to ensure detection of rapid changes in serum sodium is recommended.
Skin losses: burns
Volume losses can be extremely high in patients with significant burns, requiring urgent hemodynamic stabilization and transfer to highly specialized burn centers.[51] All patients with burns greater than 10% of total body surface area (TBSA) should be resuscitated with isotonic saline solution delivered intravenously. Advanced Burn Life Support (ABLS) Guidelines state that pediatric patients (12 years or younger) with nonelectrical burns should receive 3mL/kg/%TBSA of isotonic crystalloid (ideally lactated Ringer’s solution) in the first 24 hours. Pediatric electrical burns should receive 4mL/kg/%TBSA.[52] One half of this total volume should be delivered in the first 8 hours, and the remainder over the next 16 hours in addition to maintenance intravenous fluids.[53] Maintenance fluids should include dextrose; 5% dextrose in lactated Ringer’s solution is recommended by ABLS Guidelines. Resuscitation should be titrated hourly to urine output based on the patient’s ideal body weight. For children age >12 urine output should target 0.5 mL/kg/hour or 30-50mL/hour, and for children age ≤12 urine output should target 1 mL/kg/hour or 30mL/hour if the child is >30 kg.[52] Children with larger burns or who are hemodynamically unstable may require resuscitation in excess of these amounts. Consultation with burn specialists and transfer to a burn unit for optimal care should be considered.
Renal losses
Renal losses can be primarily water (as in diabetes insipidus) or, far more commonly, water and solutes. The most common cause of renal losses is the increased osmotic diuresis seen in children with poorly controlled diabetes. Many children present with significant volume depletion from glycosuria. Children with previously undiagnosed diabetes, very young children, and adolescents are most likely to present with significant volume depletion from diabetic ketoacidosis (DKA). Intravascular volume is best immediately stabilized and repleted with isotonic crystalloid solutions (e.g., saline). Definitive treatment of profound hypovolemia from renal losses requires adequate treatment of the underlying condition.
DKA:
Managing a young child in DKA can be complicated by late presentation, new diagnosis, and underestimation of degree of illness. High insulin sensitivity can result in hypoglycemia following treatment.[9] Patients should be stabilized by giving isotonic saline, followed by consultation with a pediatric endocrinologist, emergency physician, or intensivist.[54] Insulin therapy guided by specialist protocols is required.
Giving insulin subcutaneously to young children presenting in DKA, particularly with a new diagnosis of diabetes mellitus, is not advised.
In these patients, dehydration is mostly due to renal water loss as associated with glycosuria. A pediatric patient presenting with DKA can be estimated to have 5% to 10% volume depletion as a result of this loss. A reasonable approach is to administer 10-20 mL/kg of normal saline intravenously over the first 20-30 minutes, and the remaining fluid deficit plus the weight-based maintenance fluid requirement with either 0.45% or 0.90% saline, over the next 24-48 hours while monitoring closely for signs of cerebral edema.[9][55][56] Cerebral injury occurs frequently and with varying severity in children with DKA; however, evidence suggests that this is due to cerebral hypoperfusion and the hyperinflammatory state caused by DKA, rather than rapid fluid administration.[9][57]
Studies have demonstrated that neither clinician assessment nor biochemical analyses are highly accurate in assessing the severity of dehydration in children with DKA, although new-onset presentations, elevated blood urea nitrogen, and more severe acidosis are associated with more severe dehydration. Given the difficulty in assessing dehydration severity, estimating 6% dehydration in previously diagnosed diabetic patients and 8% dehydration in new-onset diabetic patients with DKA has been recommended.[58]
Once intravascular volume is reestablished, saline content of fluids may be changed to 0.45% saline to avoid persistent or developing hypernatremia and/or hyperchloremic metabolic acidosis.
Volume depletion from renal losses other than DKA in children is less common, and causes include diabetes insipidus, renal tubular concentrating defects, and diuretic overdose.
Diabetes insipidus:
Volume depletion may present in children with diabetes insipidus due to increased renal excretion of free water.
Enteral replacement of free water losses is generally sufficient. As water losses are primary, hypotonic solutions may be used.
If patients cannot tolerate oral replacement, intravenous hypotonic solution (e.g., one quarter normal saline) may be used.
Children with known diabetes insipidus also may receive intranasal desmopressin therapy.
Diuretic overdose:
Can result from accidental ingestions in toddlers or, rarely, Munchausen by proxy.
Should be treated similarly to those presenting with enteric losses. Serum electrolytes should be tested and any abnormalities corrected.
Loss into extravascular tissues
Volume depletion due to redistribution of fluid from the intravascular space to extravascular locations is less common in children than in adults. Nonetheless, significant hemodynamic compromise and death can result from conditions associated with generalized capillary leak (e.g., sepsis, anaphylaxis, nephrotic syndrome, congestive heart failure) or loss into extravascular space (e.g., ascites, pleural effusions, occult hemorrhage). Capillary leak can be further exacerbated by loss of oncotically active proteins into the extravascular space, thereby promoting further movement of fluid across the disrupted endothelial barrier. In children this is more commonly encountered in sepsis or anaphylaxis. Although technically it is not a loss of total body volume, functionally intravascular space is reduced. Symptoms and management are similar to those associated with volume depletion in the aforementioned conditions. A few important specifics are detailed regarding sepsis and anaphylaxis.
Sepsis:
Sepsis is usually associated with elements of hypovolemia from decreased intake, increased insensible losses, gastrointestinal losses, and third spacing (loss to the extravascular space).
In cases of septic shock, restoring circulating volume to ensure adequate end-organ perfusion is paramount. Pediatric Surviving Sepsis Campaign guidelines recommend that if a critical care facility is available, initial fluid resuscitation should be provided with intravenous isotonic crystalloid fluids in boluses of 10-20 mL/kg administered over the first hour until the patient has reversal of shock (i.e., a normal heart rate and BP for age, capillary refill less than 2 seconds, normal mental status, and adequate urinary output).[22] If fluid resuscitation results in new hepatomegaly or pulmonary edema, or if there are persistent signs of shock after 40-60 mL/kg of isotonic fluid has been given, vasoactive therapy should be initiated.[22]
If a critical care facility is not available and hypotension is present, pediatric Surviving Sepsis Campaign guidelines recommend that up to 40 mL/kg in bolus fluid (10-20 mL/kg per bolus) should be administered over the first hour and titrated to clinical markers of cardiac output. Fluid boluses should be discontinued if signs of fluid overload develop. In the absence of hypotension, bolus fluid administration is not recommended and maintenance fluids should be started.[22]
After obtaining blood cultures, empiric broad-spectrum antibiotics, which take into account local susceptibility and infectious patterns, should be given as soon as possible and always within 1 hour of recognition of septic shock.[22]
Common regimens include ampicillin and gentamicin in neonates and, in older children, third-generation cephalosporins, such as ceftriaxone plus vancomycin. Additional coverage for gram-negative organisms, Pseudomonas species, fungal pathogens, and resistant Staphylococcus aureus will be guided by the patient's medical history and clinical presentation.
Additionally, hemodynamic support with infusion of vasopressor agents may be required. There is no adequate evidence that any one vasopressor agent is a superior choice compared with another and specific choice may be individualized.[59]
Correction of coagulopathy and anemia may also be necessary for optimal management.
Anaphylaxis:
Patients with anaphylaxis classically manifest in distributive shock, in which severe systemic vasodilation and capillary leak causes underperfusion of vital organs despite normal total body volume status. While not technically volume depletion, the clinical presentation of a child in anaphylaxis has some overlap with patients presenting in hypovolemic shock, with altered mental status, tachycardia, and low BP.
Infants and toddlers may report age-specific symptoms of anaphylaxis that are different from older children and adults. For example, skin symptoms and subtle behavioral signs (pulling/scratching/fingers in ear, withdrawal, inconsolable crying, irritability, or clinging) may be more common in infants and younger children, while respiratory symptoms may be more common in older children.[60]
Initial acute therapy is with intramuscular epinephrine (adrenaline). This may be given by a self-injectable device.[60][61]
In addition, intravenous saline at 10 mL/kg is given (repeated as necessary to restore intravascular volume and hemodynamic stability).[61][62] The intraosseous route may be used if gaining intravenous access is not possible.
Corticosteroids are no longer advised for the initial emergency treatment of anaphylaxis or for the prevention of biphasic anaphylaxis.[63] Antihistamines should not normally be used during initial emergency treatment of anaphylaxis. However, these agents may be considered for the secondary treatment of anaphylaxis after initial treatment with epinephrine and hemodynamic stabilization (e.g., to treat urticaria and itching).[63] Refractory anaphylaxis may require ongoing vasopressor support. There is no adequate evidence that any one vasopressor agent is a superior choice compared with another.[59]
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