REVIEW URRENT C OPINION

Intravenous fluid choices in critically ill children Joseph A. Carcillo

Purpose of review To review the past year’s literature, and selected prior literature relevant to these most recent findings, regarding intravenous fluid choices in the management of critically ill children. Recent findings Twenty-eight publications were identified using the keywords pediatrics and intravenous fluid in the PubMed database. The subjects identified included intravenous fluid choices related to perioperative maintenance fluid management, rehydration for dehydration related to diarrhea losses, rehydration in diabetic ketoacidosis, intravenous fluid needs during mechanical ventilation, use of intravenous fluids as hyperosmolar agents in traumatic brain injury, isotonic fluid bolus resuscitation for sepsis-related capillary leak syndrome-induced hypovolemic shock, maintenance intravenous fluid and blood transfusion for malaria-associated euvolemic severe anemia shock, isotonic fluid and blood boluses for trauma-induced hemorrhagic shock, and isotonic fluid boluses and generous maintenance infusion for burn resuscitation. Summary Because intravenous fluid can be helpful or harmful, it can only be safely done in critically ill children when using state-of-the-art monitoring of patient volume, electrolyte, osmolarity, pH, and glucose status. Keywords hypernatremia, hypoglycemia, hyponatremia, hypotonic fluid, isotonic fluid

INTRODUCTION Most critically ill children require treatment with intravenous fluids during their ICU stay. This treatment can be life saving; however, if used incorrectly, it can be harmful. In this article, the author provides a current opinion, regarding the past year’s literature (and relevant recent literature in this regard) and others’ current opinions on intravenous fluid choices in critically ill children. As in adult medicine, there is a consensus opinion in pediatrics that use of intravenous fluids should be reserved for patients for whom the enteral route for fluid administration is either unattainable or contraindicated. As for what fluid to choose (Table 1), there are varied opinions.

DEVELOPMENTAL CONSIDERATIONS IN INTRAVENOUS FLUID THERAPY From the developmental standpoint, progression from the newborn period to childhood to adolescence to adulthood to senescence begins in the highest state of metabolism and a body composition with the highest percentage of extracellular and intracellular water, and ends with the lowest state of metabolism and body composition with the lowest percentage of extracellular and intracellular www.co-criticalcare.com

water. By contrast, electrolyte composition is similar in extracellular and intracellular water in children and adults. In regard to glucose, liver mass (glycogen stores) and muscle mass (protein stores) are least at birth making the pediatric patient less capable of maintaining normoglycemia through glycogenolysis and gluconeogeneis during fasting states. Because fluid and glucose requirements are linked to metabolism and children have higher metabolism, they also have higher intravenous fluid and glucose requirements. Children are more prone to dehydration and hypoglycemia during fasting, hypernatremia during dehydration, and hyponatremia with free water repletion. Routine intravenous fluid choices in adults should not be routinely practiced in children (with the exception of some rare frequently monitored exclusions). One should not use maintenance intravenous fluids without

Department of Critical Care Medicine and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Correspondence to Professor Joseph A. Carcillo, MD, Department of Critical Care Medicine and Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. e-mail: [email protected] Curr Opin Crit Care 2014, 20:396–401 DOI:10.1097/MCC.0000000000000119 Volume 20  Number 4  August 2014

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Intravenous fluid choices in critically ill children Carcillo

KEY POINTS  Consensus opinion is shifting toward using isotonic maintenance intravenous fluids in the perioperative period to avoid hyponatremia.  Subcutaneous administration of isotonic fluid boluses is now possible after subcutaneous hyaluronidase in children with mild-to-moderate dehydration.  Judicious administration of an isotonic fluid bolus and insulin infusion to reverse dehydration and diabetic ketoacidosis is a balancing act that attempts to decrease cerebral ischemia without inducing cerebral edema.  In order to attain negative or even fluid balance, the maintenance intravenous fluid administration infusion rate in mechanically ventilated children with lung injury should be less than in nonmechanically ventilated children.  The use of hypertonic saline is an increasingly accepted management principle in children with traumatic brain injury as a primary hypertonic therapy to prevent and reverse cerebral edema-related intracranial hypertension.

supplemented dextrose or without supplemented sodium [1].

PERIOPERATIVE MAINTENANCE INTRAVENOUS FLUID CHOICES Increased susceptibility of infants and children to dehydration and hypoglycemia has long been appreciated. Compared with adults, the allowable amount of time for nothing by mouth status is less and the dose of intravenous water and glucose is greater. Despite similar electrolyte needs, children are also at greater risk of hyponatremia than adults, in part, related to not only increased total body water content for distribution of sodium but also an increased predisposition to inappropriate secretion of anti-diuretic hormone (SIADH). Unlike adults who commonly are treated with D5W as a maintenance intravenous fluid, this is considered contraindicated in infants and children. Until recently, hypotonic D10 1/2NS with potassium chloride (KCl) or D5 1/2NS with KCl had been the routine intravenous fluid in the perioperative period. This practice has come under scrutiny. Current opinion holds that hyponatremia-associated morbidity in the perioperative period is related to SIADH. Maintenance intravenous D5NS with KCl [154 meq/l sodium chloride (NaCl)] results in higher serum sodium levels than D5 1/2NS with KCl (77 meq/l NaCl). Many now recommend that D5NS be considered the contemporary fluid of

choice. However, another opinion maintains that this practice can lead to salt toxicity not previously seen with hypotonic maintenance intravenous fluid strategies. Salt toxicity with maintenance intravenous saline can manifest as hypernatremia in children undergoing free water loss. More commonly, salt toxicity takes the form of hyperchloremia and a nonanion gap hyperchloremic acidosis. In the author’s opinion, the more ideal intravenous fluid choice to reduce the likelihood of hyperchloremic acidosis is found in dextrose-added lactated Ringer’s, Hartmann’s solution, or plasmalyte solutions. These intravenous fluid formulations are less likely to cause hyperchloremia, and in patients who have had abdominal surgery, also less likely to result in an ileus due to electrolyte depletion. In any child receiving maintenance intravenous fluids, it is reasonable to measure glucose, sodium, potassium, chloride, bicarbonate, magnesium, calcium, and phosphorus levels at least daily to be certain that correct fluid choices have been made. A D10-containing solution provided at the maintenance fluid infusion rate for calorie metabolism will meet the glucose delivery needs of the patient [2–5].

REPLETION AND MAINTENANCE INTRAVENOUS FLUID CHOICES IN CHILDREN WITH DEHYDRATION Dehydration remains the most common cause of fluid and electrolyte disturbance-related critical illness in children globally. Total body water is 60%; therefore, when a 3 kg baby develops diarrhea, 10% dehydration happens with a 180 ml loss of water through diarrhea. More commonly than not, children with diarrhea-related dehydration also have hypernatremia or hyponatremia. In the case of hypernatremia, the intravenous fluid composition and rate chosen is directed to replace half of the free water loss in the first 8 h and then the other half in the next 24 h. Sodium levels are frequently followed as the initial use of dextrose-containing saline (0.9%) solution not uncommonly progresses to the use of dextrose-containing hypotonic saline ( 7.3 Hartmann’s solution

Na 131 meq/l

Almost physiologic solution

No dextrose

Cl 111 meq/l

No PO4

Lactate 29 meq/l

No Mg

K 5 meq/l Ca 4 meq/l pH > 7.3 Plasmalyte

Na 140 meq/l

Most physiologic solution

No dextrose

Cl 98 meq/l

No Ca

Acetate 27 meq/l

No PO4

Gluconate 23 meq/l K 5 meq/l Mg 3 meq/l pH > 7.3 5% albumin

Albumin

Good for hypoalbuminemia-related hypooncotic states such as cirrhosis, nephrosis, and protein-losing enteropathy states

Hyperchloremic acidosis

5 g/100 ml

(I treat this with

Na 140–150 meq/l

NaHCO3)

Cl 140–150 meq/l

No dextrose

K < 2 meq/l

No other electrolytes other than NaCl and KCl

KCl, potassium chloride; NaCl, sodium chloride; NaHCO3, sodium bicarbonate.

symptoms, the goal is to increase the serum sodium by no more than 1 meq/l/h to prevent the development of pontine myelinosis syndrome. Because patients with dehydration not uncommonly have renal dysfunction, the ready-made intravenous fluids with KCl are a second choice to dextrose–NaCl solutions to which varying concentrations of KCl can be added. The most current work and opinion on rehydration of moderate dehydration relates to investigations of the successful use of subcutaneous hyaluronidase to allow clysis with intravenous fluid using a 20 ml/kg 0.9% NaCl bolus without need for intravenous access. This technique is already commonly used for administering outpatient intravenous immunoglobulin to patients on chronic 398

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replacement therapy. Adaptation of this clysis technique to the fluid management of dehydration has great implications for the global health of children [6–8].

REPLETION AND MAINTENANCE INTRAVENOUS FLUID CHOICES IN CHILDREN WITH DIABETIC KETOACIDOSIS Children more commonly present with critical illness related to type I diabetes mellitus than do adults, although the incidence of mixed type I/type II disease is increasing. New-onset diabetic keto acidosis (DKA) patients usually experience delayed diagnosis with severe dehydration due to prolonged Volume 20  Number 4  August 2014

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Intravenous fluid choices in critically ill children Carcillo

polyuria. Controversy in intravenous fluid choice and management is being investigated in an ongoing study by the Pediatric Emergency Care Research Network. The present teaching is to correct dehydration and ketoacidosis somewhat slowly. The major concern is that since it is known that children with DKA present in a hyperosmolar state related to hyperglycemia, and death during management can be related to cerebral herniation, herniation, perhaps, could be prevented if serum osmolality were corrected slowly by giving insulin and fluids cautiously. The opposing opinion worries that delaying fluid repletion too much will exacerbate cerebral ischemia related to severe dehydration and will result in impaired long-term neurologic function. This opinion holds that one can be too cautious with slow rehydration strategies. Currently, in DKA patients with dehydration, normal saline is used as the rehydrating intravenous solution. A bolus is given slowly over 1 h and then an infusion of 0.9% saline with 20 meq/l of KCl and 20 meq/l of potassium phosphate (KPO4) is run at a rate calculated to correct free water losses (see above). Insulin is started as an infusion after the fluid bolus and serum sodium, glucose, potassium, phosphorus, pH, and osmolarity are measured hourly. When glucose levels reach 250 mg/dl, then a two intravenous fluid bag technique is used with D10 running in one and the NaCl/KCl/KPO4 solution running in the other. The glucose infusion is titrated to keep glucose levels greater than 100 mg/dl until the DKA resolves. The goal is to see the serum sodium levels rise while the serum glucose levels decrease. The increasing osmolarity associated with increasing sodium offsets the decreasing osmolarity associated with decreasing glucose. A common problem encountered with this approach is the development of very significant hyperchloremic acidosis related to the use of normal saline. Hyperchloremic acidosis and diabetic ketoacidosis can cause life-threatening acidosis-induced hyperkalemia. Intravenous fluid choices must be adjusted to prevent this. Adjustments include removal of KCl and KPO4, use of hypotonic fluids such as 1/2NS rather than the normal saline or the use of more physiological choices with lower chloride but high sodium concentrations such as lactated Ringer’s, Hartmann’s solution, or plasmalyte [9–12].

MAINTENANCE INTRAVENOUS FLUID CHOICES IN CHILDREN WITH RESPIRATORY DISTRESS AND CHILDREN ON MECHANICAL VENTILATION Respiratory distress and respiratory failure require intravenous fluid choice considerations. Status asthmaticus and bronchiolitis, the most common

causes of respiratory distress, are obstructive airway diseases marked by tachypnea, prolonged expiration, and acidosis. Use of dextrose-containing 0.9% NaCl can be problematic in this population because of resultant hyperchloremic acidosis. This nonanion gap acidosis increases the drive to increase minute ventilation to compensate for metabolic acidosis. With increased tachypnea, more air trapping ensues because there is not enough time to fully exhale during the prolonged expiratory process. This worsens respiratory distress due to increasing hyperinflation. In this population, it is better to use the more physiologic intravenous solutions with lesser chloride concentration including dextrose-added lactated Ringer’s, Hartmann’s solution, and plasmalyte. These solutions allow for higher sodium concentrations with less hyperchloremic acidosis. Acute lung injury and acute respiratory distress syndrome is marked by increased extravascular lung water. Outcome in these patients is related to fluid status. Fluid overload is associated with poor outcome whereas negative fluid balance is associated with good outcome. When possible, the enteral route is preferred for maintenance hydration and nutrition. However, when this is not possible, intravenous fluids should be administered at ‘ventilator maintenance’ rather than full maintenance. The ventilator reduces the intravenous fluid requirements through three mechanisms: it reduces insensible water losses through its humidification system, it induces SIADH reducing self-diuresis, and it reduces metabolism that reduces requirement for water and glucose. The sensible remedy for this is to use a dextrose-containing solution with 0.9% saline or one of the other more physiological solutions at two-third of the maintenance rate generally recommended for children who are not mechanically ventilated. In addition, routine scheduled diuretics are likely required. The goal is to achieve daily even or negative fluid balance as measured by daily weights or ins and outs [13,14].

MAINTENANCE INTRAVENOUS FLUID CHOICES IN CHILDREN WITH TRAUMATIC BRAIN INJURY A great deal of variability exists in the management of traumatic brain injury, the leading cause of death and disability in the US children. The prevailing opinion is that 0.9% saline should be used as the maintenance intravenous fluid to attempt to keep the patient’s blood isotonic and iso-osmolar in an effort to reduce cerebral edema and prevent intracranial hypertension. In patients with intracranial pressure monitoring and intracranial hypertension (>20 cm H2O), many will run hypertonic saline

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Intravenous fluids

intravenous fluids to attain higher than normal serum sodium levels as a hyperosmotic therapy to reverse intracranial hypertension. In patients undergoing cerebrospinal fluid drainage, the loss of sodium in the cerebrospinal fluid will also require replacement with sodium-rich intravenous fluids. This is the only group of critically ill children for whom some recommend not using dextrose in the initial maintenance intravenous fluids. Under these circumstances, glucose levels are monitored hourly and dextrose is added to the intravenous solution only when glucose levels go below 70 mg/dl. Those who promote this zero dextrose strategy do so only for traumatic brain injury and not for other forms of brain injury [15,16].

INTRAVENOUS FLUID MANAGEMENT OF SEPSIS ASSOCIATED WITH CAPILLARY LEAK SYNDROME AND HYPOVOLEMIC SHOCK AND WITHOUT Over the past two decades, UK investigators have examined the role of intravenous fluid choices on survival from three forms of severe infection in three different areas of the world, resource-rich London and resource-poor Vietnam and Sub-Saharan Africa. In London, they demonstrated in children with meningococcal septic shock, a process characterized by capillary leak-induced hypovolemia, that a fluid bolus of 4% albumin followed by intubation and mechanical ventilation, infusion of a peripheral inotrope, and transfer to a PICU for further management improved survival from 78 to 98%. In Vietnam, they demonstrated in children with dengue shock, a self-limiting viral process characterized by capillary leak syndrome-induced hypovolemia, that regardless of intravenous fluid choice (lactated Ringer’s, 6% dextran 70, or 6% hydroxyethyl starch), 100% survival was attained with a fluid bolus and concluded that lactated Ringer’s was the superior fluid choice. In Sub-Saharan Africa, a region endemic for severe malaria anemia characterized by acute or chronic anemia and euvolemia rather than capillary leak syndrome-induced hypovolemia, improved survival was observed with use of maintenance intravenous fluids and blood transfusion for hemoglobin less than 5 g/dl (93%) compared with a bolus of isotonic crystalloid or albumin and blood transfusion for hemoglobin less than 5 g/dl (survival 90%). These results are quite remarkable considering that the patients in Vietnam and in Sub-Saharan Africa had no access to mechanical ventilation, inotropes, or monitoring. The Dutch have reproduced the UK meningococcal septic shock findings with the same approach, showing improvement in survival from 80 to 99%. Several 400

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groups in Southeast Asia had similar findings in dengue shock showing 100% survival with isotonic fluid boluses regardless of type. Three US children’s hospitals have shown reduction in the length of stay and survival rates of 95–98% when isotonic crystalloid boluses and antibiotics were administered in the first hour in all comer septic shock. Children’s Hospital of Boston most recently reported that a quality improvement program commenced in the first hour and focused on intravenous fluid delivery as a key driver improved compliance to Pediatric Advanced Life Support Septic Shock Five-Point Guidelines from 19 to 100% with an observed reduction in mortality from 4.8 to 1.7%. My interpretation of these studies is that isotonic fluid boluses can be effective for hypovolemic shock; however, in acute or chronic anemic shock, one should give maintenance intravenous fluids and blood transfusion, not an intravenous fluid bolus. Of course when administering fluid boluses, it is very important to make sure that the child is not or does not become fluid overloaded. Fluid boluses should not be given to children with hepatomegaly, cardiomegaly, rales, acute or chronic hemolytic anemia, or high central venous pressures attributable to fluid overload states. Several scholars do not agree with my interpretation and instead believe that intravenous fluid boluses are harmful even in hypovolemic septic shock patients. A multiple center study evaluating the effect of administering isotonic crystalloid fluid boluses and antibiotics in the first hour of septic shock presentation is presently in progress in a network of US children’s hospitals’ emergency departments [17–26].

INTRAVENOUS FLUID CHOICES IN TRAUMA AND BURN RESUSCITATION Resuscitation guidelines for traumatic shock and burns call for use of lactated Ringer’s or normal saline boluses as the initial resuscitation with monitoring of glucose levels and addition of dextrose to maintenance fluids. Massive hemorrhagic shock requires blood transfusion with packed red blood cells, fresh frozen plasma, and platelets at a 1:1:1 ratio. In burn resuscitation, the modified Parkland formula is initially used and then the 4–2–1 approach for maintenance intravenous fluid (4 ml/kg/h for first 10 kg, 2 ml/kg/h for second 10 kg, and then 1 ml/kg/h for every kilogram thereafter) is used. The goal is to avoid hypovolemia and fluid overload [27,28].

Conclusion Intravenous fluid treatment decisions vary according to disease states in critically ill children. Fluid Volume 20  Number 4  August 2014

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Intravenous fluid choices in critically ill children Carcillo

status (hypervolemia, euvolemia, or hypovolemia), glucose levels, and electrolyte levels should be routinely monitored at regular intervals in critically ill children during intravenous fluid therapy to attain optimal effects without harm. Bot intravenous fluid composition and quantity of infusion should be adjusted accordingly on an evolving basis. Acknowledgements None. Conflicts of interest The work of the author has been funded by the National Institutes of Health. The author is the Chair for the American College of Critical Care Medicine Clinical Parameters for Hemodynamic Support of Newborn and Pediatric Septic Shock, and the Pediatric Subgroup of the Surviving Sepsis Campaign. The author is also the Cochair of the World Federation of Pediatric Intensive and Critical Care Societies Global Sepsis Initiative.

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Intravenous fluid choices in critically ill children.

To review the past year's literature, and selected prior literature relevant to these most recent findings, regarding intravenous fluid choices in the...
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