Case Continued:  Clinically, you determine that Julius (2-year-old boy with an acute diarrheal illness) needs IV fluid resuscitation. Why give fluid?

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When given for acute resuscitation (maintenance fluid will be addressed later), the goal of fluid administration is to reverse and correct circulatory insufficiency (Arikan et al, 2008).

  • In physiologic terms, fluid therapy rests aims to restore and/or increase oxygen delivery
    • Oxygen Delivery = CO x CaO2, where CO is the cardiac output (determined by heart rate and stroke volume) and CaO2 is the oxygen carrying capacity (determined by SaO2 and Hemoglobin).
    • The goal of administering fluids is to increase preload, which in turn increases stroke volume and ultimately oxygen delivery
      • THUS, each time fluid is administered, the goal is to increase stroke volume.
      • NOTE: the assessment of “fluid responsiveness” is a large topic, and will not be addressed later

Furthermore, many studies have illustrated an improvement in patient outcome with early administration of IVF (Mederios et al, 2015)- more on this later.

What to give: Theory  professor

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  • Fluids are divided into 2 main categories: Crystalloids and Colloids
    • Colloids are defined as “fluids containing high molecular weight substances that remain in the intravascular compartment, thereby generating an oncotic pressure.” (Mitra et al, 2009)
      • Examples include: synthetic starches and albumin (natural)
    • Crystalloids are salt solutions of varying composition
      • In clinical practice, examples would include 0.9% saline solution, Ringer’s Lactate, and Hartmann’s solution (see Fluid Therapy: Part I for solution components)
        • Historical Note (Myburgh, 2014): “Normal Saline” was determined in the 1880s via experiments in lysing red blood cells, which indicated the amount of salt in human blood was 0.9%. Unfortunately, these studies were flawed and physiologically, human plasma is closer to 0.6% saline. Despite these findings, “normal” saline remains ubiquitous.
  • The choice of resuscitation fluid relies on Starling’s other formula, describing the determinants of fluid movement across semipermeable membranes (Myburgh, 2014)
    • The ideal solution would remain completely within the vascular space, with little extravasation into the interstitium
      • Based on this, colloids were initially thought to carry a theoretical benefit including: more rapid plasma expansion and correction of oncotic pressure (Medeiros et al, 2015)
  • Recent experiments into the glycocalyx layer of vascular endothelium have complicated this picture, indicating that in septic shock, damage to this layer contributes to vascular permeability, thereby limiting the benefits of colloids in actual practice

How does this theory play out in the real world?

In other words, in patients presenting with hypovolemia and/or shock, what fluid should be given to restore intravascular volume?

  • Colloids vs. Crystalloids
    • From our theoretical perspective, it would seem that colloids, though markedly more expensive, would be better
    • Pediatric-centered data is sparse, but studies comparing colloids and crystalloid in septic shock (usually dengue), fail to show convincing benefit of one solution over another (Mederios et al, 2015)
      • A recent meta-analysis of adult patients with sepsis indicates that synthetic colloids, specifically 6% HES, are associated with a higher rate of renal replacement therapy and mortality (Gattas et al, 2013)
      • Conversely, in adults, the use of albumin compared to crystalloid trends towards showing a 90 day mortality benefit  (Xu et al, 2014)
  • Chloride rich vs. balanced salt solutions
    • Recently, researchers have turned their attention to comparing chloride rich (e.g. normal saline) solutions with more physiologically balanced solutions (Ringer’s Lactate or Plasma-lyte)
      • These studies arose from observational studies showing (again, in adults) that hyperchloremia is associated with acute kidney injury (Suetrong et al, 2016)
        • In the recent SPLIT trial (randomized trial comparing NS and plasma-lyte), investigators failed to show any differences between the groups. In this study, the primary outcome was AKI, with secondary outcomes being use of RRT and in-hospital mortality (Young et al, 2015)
    • While such literature is sparse in the pediatric world, numerous case reports detail the association with normal saline and hyperchloremic metabolic acidosis (Skellett S et al, 2000).

Until further studies are performed, crystalloids should be used as first line therapy in fluid resuscitation in pediatrics, with attention paid to avoiding large volumes of chloride-rich fluids.

 

Now that we’ve chose a fluid, how to administer?

  • By convention, pediatric patients are given fluid boluses in 20 ml/kg aliquots. Unfortunately, the literature detailing how “20cc/kg” came to be is sparse.
  • The 2015 PALS (pediatric advanced life support) Guidelines indicate that in patients with signs of shock (diminished pulses, cool/pale/mottled skin, prolonged capillary refill, tachycardia, and altered mental status (particularly ominous), 20cc/kg should be administered over 5-10 minutes
  • In the United States, various studies have shown adherence to the PALS guidelines in children with shock is correlated with improved mortality (Carcillo et al, 2002; Han at al, 2003) and shorter length of stay (Paul et al, 2012)
  • However, the recent FEAST study (RCT Trial, population: children in sub-Saharan Africa), showed fluid bolus therapy was associated with increased mortality (Maitland et al, 2011).
    • Presently, Canadian investigators (SQUEEZE Investigators) are investigating this question (fluid sparing vs. usual care) with results of their pilot studying informing the feasibility of a multi-center trial (Parker et al, 2016).

 

Conclusions

  • Fluid, like any other intervention, has indications and contraindications
  • When deciding to give fluid boluses, determine the underlying pathophysiologic insult (sepsis vs. hypovolemia from ongoing losses) and intervene appropriately
  • Anticipate complications (fluid overload, metabolic derangements)
    • Case control studies from single institutions indicate that in the PICU setting, fluid overload is associated with higher morbidity (Sinitsky et al, 2015) and mortality (Sutawan et al, 2016).
    • Hyperchloremic metabolic acidosis with normal saline
  • Various retrospective studies show that adherence to PALS algorithm is associated with improved outcomes

 

Faculty Review: Lee Polikoff, MD

 

References

  • Arikan AA et al. “Pediatric Shock.” Signa Vitae. 2008;3(1)13-23
  • Carcillo JA et al. “Clinical practice parameters for hemodynamic support of pediatric and neonatal patients with septic shock.” Critical Care Med. 2002;30:1365-78
  • Gattas DJ. “Fluid resuscitation with 6% hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: Systematic review of effects on mortality and treatment with renal replacement therapy.” Intensive Care Medicine. 2013;39(4)558-568.
  • Han YY et al. “Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics. 2003;112: 793-99.
  • Maitland K et al. “Mortality after Fluid Bolus in African Children with Severe Infection.” NEJM. 2011;364:2483-2495.
  • Medeiros DN et al. “Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.” Pediatric Emergency Care. 2015;31(11)e11- e16.
  • Mitra S et al. “Are All Colloids Same (sic)? How to Select the Right Colloid?” Indian J Anaesth. 2009;53(5)592-607
  • Myburgh JA. “Fluid resuscitation in acute medicine: what is the current situation?” Journal of Internal Medicine. 2015;277; 58–68
  • Paul R et al. “Adherence to PALS Guidelines and Hospital Length of Stay.” Pediatrics. 2012;130(2):e273-280
  • Skellett S et al. “Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid administration.” Arch Dis Child. 2000; 83:514-516
  • Suetrong B et al. “Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients.” Critical Care. 2016; 20:315
  • Sutawan IB et al. “Association of fluid overload with mortality in pediatric intensive care unit.” Crit Care Shock. 2016;19:8-13
  • Young P et al. “Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit.” JAMA. 2015
  • Xu JY et al. “Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.” Critical Care. 2014;18:702