Sepsis in the Critically Ill Child is a 2013 forty-five minute video from Dr. Adrianne Randolph available on the Open Pediatrics Site. You need to register for the site (free) to view the video. The video is in the library section. Please note that there is a tab with the complete transcript on the the video page. The text on this page is from the transcript. Comments in [ ] are mine. The resources section after the notes contains references to Dr. Randolph’s 2005 article (1) and to the FEAST trial. (2) There is also a reference to the webcast, The Pediatric Guidelines from the Surviving Sepsis Campaign: Considerations for Care, (3) from the Surviving Sepsis Campaign. And finally review Dr. Randolph’s 2014 article on pediatric sepsis. (4)
18:42 to 20:32
The interviewer, Dr. Jeff Burns, Chief of Critical Care at Boston Children’s Hospital states: So, Dr. Randolph, if I followed you accurately, the need to define sepsis was driven by two goals. The first goal was, as you noted, so that we could do more rigorous research; we had no definition and we can’t study it and look for outcomes if we can’t define it, and obviously that’s important. The second goal was in the clinical arena, as you’ve said, is that these are introductory criteria but they don’t really tell us where the patient is going. But they help us align the patient into sepsis, or severe sepsis, or septic shock as really kind of entry criteria to help me understand really how aggressive I need to be and telling me I need to be aggressive early on, depending on which cohort I’m in, or certainly be vigilant, but it doesn’t point the way forward as to where the patient is going to be in 24 or 48 hours. Is that an accurate summation of where you are?
And Dr. Randolph responds: Yes, that’s a good summary, Jeff. I think that the whole goal here is to identify early on those patients who may progress rapidly to catch them early because we know that’s where these definitions are going to have an impact. In this whole group of infected patients, only a few, you know depending on some countries, half may have a risk of mortality; other countries, a smaller proportion, may have a risk of mortality. But either way, identifying that cohort early on and by intervening in all of them, if you can’t tell the difference, as soon as you can stratify them out, great, but if you can’t tell which direction the patient is going in, give them a bundle intervention to try to prevent the inexorable progression that often occurs in those patients who have the worst forms of sepsis, who are hard to distinguish from those who have less severe infections.
22:03
Jeff, I think that the guidelines are the best we can do at the time, given the limited data that we have, but that said, I don’t think any of the authors would say that they feel comfortable that this is the best way to manage all of the patients that we see with sepsis. We need more evidence to guide us in what is a better way. Especially in the area, I think, right now, two things that are key is fluid management and antimicrobials.
First, going over fluid management, there are new data emerging from a large African study, or recent data from the FEAST trial Dr. Maitland was the lead author on that was posted in New England Journal of Medicine, and over 3,000 African children, where they categorized patients in either decompensated shock with hypotension, or most of the 3,000 kids that they randomized had compensated shock where they had the poor profusion, the poor capillary refill. They met our criteria for septic shock but not necessarily vasopressor-dependent, but what you and I would, in general, think of if I said septic shock to you. And the outcomes were clear; mortality was markedly higher, significantly higher in those patients who got fluid boluses, compared to no bolus, that was either albumin or normal saline. This was really extremely surprising to everyone in the world and it took a long time for a lot of people to believe that this is true, that there must be something in the trial; how could this happen?
It is true that over half of the children in that trial had malaria, and it’s also true that about a third of those children had profound anemia with hemoglobins of 5 or less. But despite that, no matter how they cut the data, and they published other papers afterwards, it remains that this this strategy that we assumed was beneficial, in which they extrapolated from what is somewhat known to be beneficial in treating patients with meningococcemia and early meningococcemia with this goal-directed, targeted, aggressive fluid resuscitation, really led to increased mortality. And so it really calls in to question how should we then be managing fluids in many of our patients?
25:08
The interviewer then asks Dr. Randolph: In your own practice, because I suspect there are a lot of people around the world who want to understand what you now do in your own practice in response to that study, am I correct in saying that you’re concerned at the scientific level that we need to study this further, but at a clinical level, have you changed your practice about food resuscitation because of the FEAST study?
25:32 to 27:25
Dr. Randolph replies: To be honest, I have always been treating patients who have a pulmonary source of infection more on the dry side. If they don’t have hemodynamic instability that requires me to give them fluids or vasopressors to maintain their blood pressure, I tend to just give them enough fluids to maintain urine output and perfusion and monitor other laboratory values that tell me if they have adequate perfusion, such as lactate and their BUN and creatinine. So if the patient has adequate urine output and a low lactate and has profound pneumonia, which is the majority of the septic patients we treat, many of those patients, in my practice, wouldn’t get a lot of extra fluid. In fact, I would cap them off at maintenance fluids and just give them as much; I would be at the bedside constantly titrating in fluids frequently, as needed, versus giving them these very large boluses of fluid.
There are some studies in adults showing that acute lung injury may be a preventable disease in many patients and may be related to how much fluid we give. Now is it fair to say that in hypovolemic shock, you would continue to be very aggressive with fluid? Yes, I think that it’s very important to figure out quickly, why is that patient shocky? First make sure that you identify cardiogenic shock because fluids will often make those patients worse as well. Figure out which, often certain sepsis organisms can trigger cardiogenic shock, and some patients with sepsis even can present with myocarditis and other reasons why they’re hypotensive.
28:40
Dr. Randolph: To me, fluid management is something done at the bedside- frequent checks, frequent assessment, [frequent] titration. It can’t be something that can be easily protocolized once you get [the patient] up [to the pediatric ICU] . In the initial phase, it’s important to adequately resuscitate the patient, which is why they started off with this 40 cc/kg goal of initially make sure that you have some adequate fluid resuscitation.
[So how should front-line pediatricians in our office, urgent care center, or emergency department respond to the FEAST trial? Dr. Randolph gives thoughtful advice which the interviewer restates and summarizes below.]
30:59
The interviewer says: So, Dr. Randolph, if I follow you accurately,what your emphasizing is this: that in both the definitions and the treatment, one size does not fit all, and that we need more precise definitions of sepsis. In the treatment modality, if I understand you, what you’re saying is, follow the surviving sepsis treatment guideline in the first hour and that thereafter, ongoing treatment requires an expert clinician at the bedside to use judicious management in both assessment and ongoing treatment and that each context will be a somewhat different.
31:34 to 33:56
Dr. Randolph replies: Yes, that’s exactly right, Jeff. I think that it’s [in] that first hour when you don’t know what’s going on, you have a baby who looks infected and sickly; you start with the initial resuscitation, but then it evolves. And very clearly, with your experience, you’ll figure out what it is, and with an x-ray and some of the other diagnostic capabilities that you may have, what is exactly going on. And the baby’s response to or the child’s response to that initial treatment tells you a lot. So that’s exactly right; it’s where clinical expertise comes in and categorization of the patient into different infectious syndromes, which helps you better prognosticate and treat.
32:37 to 33:56
Dr. Reynolds now turns to antibiotic therapy: Well one of the mainstays of treatment, as you know, is antimicrobial therapy and the golden hour; getting those antibiotics in in that first hour is key, or other antimicrobial-targeted organisms. One of the problems is that we have three categories of patients. We have patients who don’t have bacterial sepsis, we have patients who have bacterial sepsis with a common organism, and then we have patients with bacterial sepsis who have a resistant organism. And unfortunately, Jeff, those are some of the most highly fatal cases, and that’s a growing population in pediatrics worldwide, is this growth of resistant organisms. If you have a neutropenic patient, for example, and you pick the wrong gram-negative rod coverage because that cancer patient with fever [and] neutropenia has an organism that’s resistant to your antimicrobial, with no white blood cells, you haven’t given them any way to fight that infection. Their only way to fight that infection is picking the right agent, so you really have to know the epidemiology of your area, and you have to overshoot by focusing on these, covering these resistant organisms, like MRSA.
From 33:56 to the end at 45:16, Dr. Reynolds covers many important topics but they are topics of interest to the pediatric intensivist rather than to primary care pediatricians whose job is to promptly recognize sepsis and rapidly institute the correct therapy for the first hour until the intensivist assumes care.
Resources:
(1) International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics [Link is to PubMed Abstract]. Goldstein B, Giroir B, Randolph A Pediatr Crit Care Med. 2005 Jan;6(1):2-8.
(2) Mortality after Fluid Bolus in African Children with Severe Infection [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Maitland K, et al; FEAST Trial Group. N Engl J Med. 2011 Jun 30;364(26):2483-95. doi: 10.1056/NEJMoa1101549. Epub 2011 May 26.
(3) The Pediatric Guidelines from the Surviving Sepsis Campaign: Considerations for Care
“Too often we have heard of a usually healthy child’s complaints being attributed to “just the flu” or “he seemed out of sorts,” when early recognition of sepsis symptoms can mean the difference between life and death. Overall mortality from sepsis is much lower in children than in adults in the well-resourced setting, but specific concerns related to age-specific factors must be top of mind when treating a pediatric patient with severe sepsis or septic shock. Margaret M. Parker, MD, focuses on applying the SSC guidelines in the pediatric population.” 
Download webcast slides (Right-click and Save the file on your computer. PowerPoint Required)
(4) Pediatric sepsis: important considerations for diagnosing and managing severe infections in infants, children, and adolescents [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Randolph AG, McCulloh RJ. Virulence. 2014 Jan 1;5(1):179-89. doi: 10.4161/viru.27045. Epub 2013 Nov 13.
