SCCM Resource Library-Where Are We Now? Balanced or Unbalanced, Fluid Restrictive or Not?

Video Transcription

Hi, my name is Kelly Crowley and I am a Pediatric Critical Care Pharmacist in the Intensive Care Unit at UPMC Children's Hospital of Pittsburgh.  I hope that you are enjoying the Congress so far. Fluid resuscitation management strategies for children were updated in the Pediatric Surviving Sepsis Guidelines update in 2020.  Since that time, new publications on this topic may add clarification to some of the recommendations.  I will be speaking specifically about fluids and the application of new data in the pediatric sepsis population.  I'm going to start with a review of the Pediatric Fluid Resuscitation Management Guidelines as described in the 2020 Surviving Sepsis Campaign International Guidelines for the  Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Effective fluid resuscitation in septic shock can correct hypovolemia caused by capillary  leak, vasodilation, and fluid losses. Without maintenance of adequate atrial filling pressures, cardiac output will fall and organ perfusion will be compromised.  Recommendations in these guidelines, as with others, are based on a systematic evaluation  of available evidence leading to a characterization of the quality of that specific evidence and a strength designation assigned to each recommendation.  The Grade Approach Principles guide the classification of quality of evidence from high, which would  include systematic reviews and randomized control trials, to low, such as well-conducted prospective observational cohort studies, to very low, for example, case control studies  or case series, based on these six domains. Students performed initial assessments of quality of evidence and then incorporated  feedback from panel members to generate final evidence profiles using Grade Pro GDT.  Strong recommendations and best practice statements have the highest strength rating, with recommendations  derived from high or moderate quality evidence, meaning that most individuals should receive the recommended course of action.  Weak recommendations have any quality of evidence, and different choices are likely to be appropriate for different patients.  So returning back to the guidelines and moving on to the Pediatric Fluid Therapy Recommendations for the initial resuscitation of patients in septic shock or other sepsis-associated  organ dysfunction, this was broken down into two categories. It was dependent on whether or not intensive care unit was available within the health care system.  So health care systems with intensive care units available, recommendations are to administer  fluids as incremental boluses up to 60 milliliters per kilogram at most facilities, titrated  to clinical markers of cardiac output, and discontinued if signs of fluid overload develop. Health care systems with no intensive care unit available, the fluid management approach  is dependent on whether or not hypotension is present. Incremental boluses up to 40 milliliters per kilogram will be administered only if  blood pressures are low, otherwise fluids will be administered at a maintenance rate without boluses.  In all settings, the need for fluid administration should be guided by frequent reassessment  of clinical markers of cardiac output, serial blood lactate measurement, and advanced monitoring when available.  Signs of fluid overload that should limit further fluid bolus therapy may include clinical signs of pulmonary edema or new or worsening hepatomegaly.  The panel recommends use of balanced or buffered crystalloids rather than unbalanced for the initial resuscitation of children with septic shock.  This is largely based on evidence from adult studies, which suggests that excesses of chloride  are associated with adverse outcomes, including kidney injury and increased incidence of mortality.  To date, there are no randomized controlled comparison trials in the pediatric population. In two large observational studies in septic children, one being published by Emrath and  colleagues and the other by Weiss and colleagues, use of balanced or buffered crystalloids for the first 72 hours of admission was associated with a decrease in mortality.  That being said, 0.9% saline may be preferred in specific populations, such as patients with increased intracranial pressure or with specific indications, hyponatremia, for example.  The panel did feel that data is sufficient to say that the desirable consequences of balanced or buffered crystalloids probably outweigh the undesirable consequences of 0.9% saline.  A call to action was issued as the level and strength of evidence so far are not of high caliber.  The panel stated that the evidence gaps presented a good deal of research opportunities. So while there are recommendations in the guidelines regarding fluid resuscitation and  bolus administration, only Maitland's FEAST trial in 2011 provided high quality evidence. No new literature has been presented specifically addressing early resuscitation strategies  and bolus administration. However, there has been quite a bit of scrutiny directed towards fluid overload in the PICU patient.  The data on this slide represents initial efforts to evaluate the effects of fluid overload on outcomes.  Each trial was examining the issue from a different perspective with different hypotheses. I will be referring to each trial by the first author's name.  Moutoth analyzed patients with shock requiring inotropes and or mechanical ventilation at the 72-hour mark.  Al-Nabawi was looking to define a critical threshold for fluid overload through 28 days in all PICU patients.  Al-Obaidi's goal was to define characteristics of fluid accumulation and associations with outcomes for all PICU patients at day 5.  Lima targeted all PICU patients with expected stay greater than 48 hours to assess timing of fluid overload, whether it be early or late in the ICU stay.  And Barheit investigated non-resuscitation fluid administration volumes. Now I did emphasize that these are all PICU patients. These were not limited to strictly sepsis patients.  The comparison table describes the mortality rate and percentage fluid overload, or PFO, of non-survivors from each.  Taking the variations in trial specifics and timing between the five trials into account, no direct comparisons can be made.  However, the results do suggest that non-survivors are receiving substantial amounts of fluids and often become greater than 10% fluid overloaded during their PICU admissions.  Additionally, there may be some timing considerations to factor in. Al-Obaidi noted that non-survivors experienced longer durations of fluid overload with odds  ratios increasing as PFO increased. Lima observed in their greater than 20% PFO cohort, there were no deaths in those peaking  within the initial 48 hours of treatment, but a 24% mortality rate if PFO peak occurred later than that.  Al-Obaidi et al., in a separate publication, performed a systematic review that included a mix of retrospective cohort studies, prospective cohort studies, case control studies, and  a secondary analysis of a randomized trial. Their objective was to describe methods of measuring fluid balance, define fluid overload,  and evaluate association between fluid balance and outcomes in the critically ill pediatric patient.  Although the primary outcome of the meta-analysis was mortality, this table is focusing on secondary  outcomes associated with fluid overload, specifically treatment intensity, organ failure, and resources used. As you can see, all were much higher when fluid overload was present.  So the other big question is fluid composition. This slide is showing a comparison chart of the composition of various crystalloid fluids in plasma.  Hartman's solution is the European version of lactated ringers, and here we see that the balanced fluids are much more similar to plasma in makeup than the 0.9% sodium chloride  or normal saline. In 2021, Trapacia, Korn, and colleagues conducted a randomized control trial exploring the use  of balanced salt solution versus normal saline for resuscitation in a pediatric sepsis cohort. They sought to compare outcomes and adverse effects of pediatric sepsis resuscitation  with the use of the different solutions for fluid bolus therapy. 42 patients were randomized to one of three treatment arms, normal saline, lactated ringers,  or stereofundin, which is an isofluid manufactured in Germany. Patients with pre-existing renal or hepatic impairment, end-stage disease, or multiple  organ dysfunction syndrome were not included. Salt samples were collected at initial 2, 6, and 24 hours, and urine samples were collected  at initial and 2 hours to perform the urinary neutrophil gelatinase-associated lipocalin analysis. The results are listed on this slide.  No difference was found among the three groups regarding arterial pH, base excess, serum lactate, central venous saturation, lactate clearance, or base excess change over time.  The present study did not show any difference regarding serum sodium, chloride, potassium, ionized calcium, ionized magnesium levels, or change in serum chloride level at any points  of measure. No difference could be observed regarding cumulative fluid after fluid bolus therapy. Other renal outcomes did not differ significantly among groups.  No association was found among types of fluid in the abnormal coagulation study, serious bleeding, or requirement for blood product transfusion.  In the present study, different types of fluid bolus therapy did not correlate with any of the PICU outcomes.  The author discussion does state that this present study added prospective randomized control trial data in this specific group of pediatric sepsis population, supporting  the surviving sepsis panel recommendations, and made evidence slightly more solid.  Another 2021 publication, this one by Barheit, looked at the effects of an initiative to transition from saline to balanced fluids as the standard of care for resuscitation  and maintenance fluids administration in all patients admitted to the PICU at Ann and Robert H. Lurie Children's Hospital between August of 2018 and March of 2020.  Both time periods had similar admission sources, primary diagnosis, and rates of immune compromised state and septic shock. Some demographic information is shown here.  So this chart shows the post-intervention effect of the balanced fluid initiative on serum chloride profiles and the adjusted risk ratios.  Patients were much less likely to become hyperchloremic post-intervention. Other outcome results from the Barheit study are shown here.  Risk of kidney injury, mortality, ventilator days, renal replacement therapies, and length of stay were all very similar between the groups.  Excursions outside of the normal serum chloride range were associated with more kidney injury and ventilator days, but only hyperchloremia had increased odds of mortality.  Additionally, I did take a peek at the clinical trials registry to see what might be coming down the pike in the future.  The PROMPT-BOLUS trial is a multi-center pragmatic clinical trial to compare the effectiveness  and relative safety of balanced fluid resuscitation versus 0.9% normal saline in children with  septic shock, including whether balanced fluid resuscitation can reduce progression of kidney injury.  The Balanced Crystalloid vs. Saline in Children with Septic Shock trial is a comparison of  the incidence of acute kidney injury in children resuscitated with either balanced or buffered versus non-buffered fluids.  The SQUEEZE trial's purpose is to determine which fluid resuscitation strategy results in the best outcomes for children treated for suspected or confirmed septic shock.  In this study, eligible children will be randomized to either the usual care arm or the fluid sparing arm.  The PRECISE trial is evaluating the effects of mini-BOLUS fluid to predict response to fluid expansion in pediatric septic shock.  Investigators in the Balanced Crystalloid vs. Saline in Children with Septic Shock trial are comparing the effects of solutions on the incidence of acute kidney injury in children  resuscitated with either of the fluids to attempt to answer the question of which one could be preferred for resuscitation.  So, in conclusion, with regards to fluid volumes, the fluid resuscitation recommendations in the Surviving Sepsis Campaign International Guidelines continue to be the most current.  Fluid intake throughout the PICU length of stay seems to be emerging as an important factor after resuscitation. One may consider conservative fluid administration as appropriate.  With regards to fluid composition, balanced crystalloids remain as the preferred option for resuscitation in pediatric sepsis management.  Evidence suggests that balanced fluids for post-resuscitation maintenance improve electrolyte profiles.  Of the commercially available options, there is not a preferred balanced crystalloid solution for either resuscitation or maintenance fluids.

Video Summary

The video provides an overview of fluid resuscitation management strategies for children with sepsis. It discusses the Pediatric Surviving Sepsis Guidelines update in 2020 and highlights the importance of effective fluid resuscitation to correct hypovolemia and maintain adequate atrial filling pressures. The guidelines recommend administering incremental boluses of fluids up to a certain volume based on the presence or absence of an intensive care unit. The panel also recommends the use of balanced or buffered crystalloids over unbalanced crystalloids for the initial resuscitation of children with septic shock, although there is limited evidence specifically in the pediatric population. The video also touches on the issue of fluid overload in the pediatric intensive care unit (PICU) patients, and the potential benefits of balanced fluids for post-resuscitation maintenance. Finally, it mentions ongoing clinical trials that aim to further evaluate the effectiveness and safety of different fluid resuscitation strategies in children with sepsis.

Asset Subtitle

Sepsis, Pediatrics, 2022

Asset Caption

The updated pediatric sepsis guidelines were published in early 2020. Many recommendations were based on low quality of evidence, thus making some clinicians unsure of whether or when to employ them. Since early 2020, several studies have been ongoing that may help clarify some of the guideline recommendations, specifically in the areas of fluids, steroids/metabolic support, and parenteral nutrition. This session will provide synthesis of study results regarding these therapies and will help attendees understand whether and how these therapies are best utilized in the pediatric sepsis population.

Meta Tag

Content Type Presentation

Knowledge Area Sepsis

Knowledge Area Pediatrics

Knowledge Level Foundational

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Fluids Resuscitation Management

Tag Pediatrics

Year 2022

Keywords

fluid resuscitation

children

sepsis

Pediatric Surviving Sepsis Guidelines

hypovolemia

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