Surviving Sepsis - APSA Practice Gaps 2019

This one uh was a practice gap again that we felt from the PDC to uh bring up. It was we discussed it at the America at the Appsa meeting this year. So, the vignette is that of a 9-month-old boy who presents to the emergency room with a history of being lethargic, has a temperature of 39.8°C, so it's febrile, has uh his tachycardic at 180, has a systolic blood pressure of 60, so is somewhat hypotensive with warm extremities. Um, during the course of that ED visit, uh he gets intubated and uh receives a total of 60 cc's of normal saline uh boluses, uh 60 cc's per kilo uh over 320 cc per kilo boluses. Uh, his hemoglobin on evaluation was 12 grams per deciliter. So, at this point, uh you note that he continues to have a systolic blood pressure in the 60s despite those boluses and you did administer broad spectrum antibiotics uh during this first hour that this child was in the uh I in ED. So, according to the the sepsis guidelines, um, from the Surviving Sepsis Campaign, the next best step is um, to start an epinephrine infusion. And the what they say in in their guidelines, uh which first came up in 2004, modified in 2008, just think of it as it comes with every every Olympics. The last time it was uh modified was in 2016. Uh the latest pediatric guidelines are 2012 and they talk about the importance of fluid bolus. So, one, recognize that this is a child who may have sepsis. Two, initiate fluid management. Three, initiate broad spectrum antibiotics. Four, if they may are still hypotensive despite the fluid boluses, at that point you must consider initiating vasopressors. The question then is which vasopressor should you use? And um, in adults, it's actually Nor epinephrine is the vasopressor of choice. For children, uh, for the longest time dopamine used to be our fallback for when we we wanted to use a vasopressor. Uh there are two randomized trials that have been recently concluded which showed that when you compare dopamine with epinephrine, which was the the comparison, uh actually mortality was better in one of the studies for those who were randomized to Epi. And in the other study, Epi had a better um, improvement or more rapid and sustained improvement in the systolic blood pressure complaint compared to dopamine. So, epinephrine is probably of the of the choices epinephrine will be the treatment of choice. Others would say, what about vasopressin? There's some good uh adult data to suggest that the use of vasopressin or vasopressin-like drugs um can be very efficacious in increasing their blood pressure. Um, in pediatric trials, they've just been too few and not randomized, therefore, the data is not there yet. So, we have to stay tuned for that. Um, the next final question is where is what is the role of hydrocortisone? And so in fact, in the Surviving Sepsis Campaign, there is a role for hydrocortisone and that is for patients who are vasopressor refractory, meaning you started vasopressors and their systolic blood pressure remains low, the next algorithmic step is to consider hydrocortisone for vasopressor um recalcitrant um um blood pressure issues. Okay. And we also have a question from the audience uh from Dr. Barley on there was a question about uh for Duodenal atresia specifically, um, starting preoperative antibiotics uh because they would do that because of the risk for bacterial translocation. So, they were wondering why you wouldn't give preoperative antibiotics for Duodenal atresia. So, the reason that we would not is because we would take the child to the operating room on a fairly not, I want I don't want to say urgent, but on an expeditious basis. So, um babies with duodenal atresia at our institution go to the OR the next morning or as soon as their echo is done. And I guess that would depend upon how long they think it's going to be before they can get the child to the operating room. Okay. So, again it just this just goes up to showing what the uh sepsis pediatric sepsis guidelines are which were from 2012. You give 20 cc per kilo boluses of isotonic fluid, in this case saline, or you can give colloid if you choose to do so, like albumin. Uh, up to 60 ml per kilo. Um, your goal is perfusion improvement. So, with this, with at 40 cc per kilo, if you're seeing perfusion improvement, you don't have to give the third bolus. You your goal is to see perfusion improvement. Um, you stop if you're seeing over perfusion. For example, patients develop um uh rales on auscultation or their liver gets large and enlarged. You must start antibiotics. Um, there's data to show in adults especially that if you wait over 3 hours to start start antibiotics in a patient who's septic, uh and they're all these are all empiric antibiotics that your your survival goes down. So, you must do that. If their hematocrite is or hemoglobin is less than 10, then a transfusion may be indicated in this particular scenario uh because of uh they're actively being septic. There is no role for activated protein C uh in this situation. So, again, sepsis guidelines recognize flow fluids, antibiotics and vasopressors if needed, all within the first hour. The question from Dr. Harmon was is is the recommendations on which antibiotics? The recommendation is broad spectrum. So, you want to cover pretty much everything. Um, think something like an extended spectrum penicillin like uh um piperacillin tazobactam or ampicillin sulbactam. Uh, something which is again very broad spectrum. You want to cover everything. It's empiric. So, you want to cover everything. And if you're concerned about fungal infection, throw that in as well. Um, so broad spectrum antimicrobial therapy. And in terms of cultures, uh, I know in the adult world we say try to get them before we start antibiotics, but don't delay starting the antibiotics if you're waiting for the. No, that that's a great question and that's a great point. Um, the the revised guidelines in adults came out last year, 2016 uh and in fact emphasized that you draw blood and you draw blood for a few things, one to check a lactate level, two, to send uh cultures just prior to starting the antibiotics. You don't wait, but you want to send those cultures as soon as possible because that led everybody in the previous sepsis campaigns, it led to patients being on antibiotics, broad spectrum antibiotics for a very prolonged period of time. And so what came up as a subsequent recommendation was antibiotic stewardship, as Dr. Barley mentioned, um in her previous discussion that you follow those cultures and titrate those antibiotics down or stop them all together if in three or four days these patients have improved and it's no longer an infectious issue. Thank you. Salim, I think the other one more thing that you might want to talk about or you may want to mention is surviving sepsis source control. So, where does that fall in on the Surviving Sepsis Campaign? So, the adult Surviving Sepsis Campaign, which was revised, talks about managing infection, uh managing resuscitation, using ventilation where required and then finally system improvement. When you talk about the manage infection part, uh antibiotics is just one thing, source control is key. So, if you have an abscess, if you have uh somebody who has a perforated appendicitis or uh something of that nature, source control is key. And as the third part of manage infection, they introduced antibiotic stewardship as part of the whole deal. Um, in fact, the odds ratio for in one study for not starting antibiotics within 3 hours in children was a 3.92 odds ratio of dying. Almost four times likely to die. Uh and then same thing with manage resuscitation, fluids, you have a target uh mean arterial pressure target and the use of vasopressors. So, these these steps have been shown to clearly reduce mortality in patients with sepsis. And then of course, now we have to deal with when they've survived sepsis, which now a lot more are, what are the consequences of that and now we're there's more discussion on the consequences of sepsis. Perfect. Can I ask one more thing? So, Salim, can you can you discuss or give us a little bit of an idea of where ECMO falls in on this uh surviving sepsis issue? That's a great question. And so, the as you keep going down that that uh pathway when you so in patients who have not responded to vasopressors. They're still hypotensive. You start hydrocortisone, you give bolus and they still are hypotensive at that point. Um, warm or cold uh you know irrespective. If they're still hypotensive at that point, uh three things have been brought up as adjuncts. One is extracorporeal life support or ECMO. Uh the other is the use of what is the use of renal replacement therapy and three, the use of plasmapheresis as an adjunct in the situation. Of the three, the one that's been studied the most and is still in use is extracorporeal life support. And it's not formally mentioned in the sepsis guidelines, but it certainly is there as an adjunct so that in in institutions where you have the ability to use ECMO or uh extracorporeal life support that in those patients who are still not responding uh to initiate and consider ECMO in that situation. The survival for patients who went on ECMO with severe sepsis with recalcitrant hypertension is about 46% overall when you look at as all comers, which is better than zero.