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LJUBLJANA, SLOVENIA – The dogma of the “Golden Hour” for the immediate management of pediatric sepsis has been oversold and actually is based upon weak evidence, Luregn J. Schlapbach, MD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.
The true Golden Hour – that is, the time frame within which it’s imperative to administer the sepsis bundle comprised of appropriate antibiotics, fluids, and inotropes – is probably more like 3 hours.
“The evidence suggests that up to 3 hours you don’t really have a big difference in outcomes for sepsis. If you recognize shock there’s no question: You should not even wait 1 hour. But if you’re not certain, it may be better to give up to 3 hours to work up the child and get the senior clinician involved before you make decisions about treatment. So I’m not advocating to delay anything, said Dr. Schlapbach, a pediatric intensivist at the Child Health Research Center at the University of Queensland in South Brisbane, Australia.
The problem with a 1-hour mandate for delivery of the sepsis bundle, as recommended in guidelines by the Surviving Sepsis Campaign and the American College of Critical Care Medicine, and endorsed in quality improvement initiatives, is that the time pressure pushes physicians to overprescribe antibiotics to children who don’t actually have a serious bacterial infection. And that, he noted, contributes to the growing problem of antimicrobial resistance.
“You may have a child where you’re not too sure. Usually you would have done a urine culture because UTI [urinary tract infection] is quite a common cause of these infections, and many of these kids aren’t necessarily septic. But if people tell you that within 1 hour you need to treat, are you going to take the time to do the urine culture, or are you just going to decide to treat?” he asked rhetorically.
Dr. Schlapbach is a world-renowned pediatric sepsis researcher. He is far from alone in his reservations about the Golden Hour mandate.
“This is one of the reasons why IDSA [the Infectious Diseases Society of America] has not endorsed the Surviving Sepsis Campaign,” according to the physician, who noted that, in a position statement, IDSA officials have declared that discrimination of sepsis from noninfectious conditions remains a challenge, and that a 60-minute time to antibiotics may jeopardize patient reassessment (Clin Infect Dis. 2018 May 15;66[10]:1631-5).
Dr. Schlapbach highlighted other recent developments in pediatric sepsis.
The definition of adult sepsis has changed, and the pediatric version needs to as well
The revised definition of sepsis, known as Sepsis-3, issued by the International Sepsis Definition Task Force in 2016 notably dropped systemic inflammatory response syndrome (SIRS), as a requirement for sepsis (JAMA. 2016;315[8]:801-10). The revised definition characterizes sepsis as a dysregulated host response to infection resulting in life-threatening organ dysfunction. But Sepsis-3 is based entirely on adult data and is not considered applicable to children.
The current Pediatric Sepsis Consensus Conference definition dates back to 2005. A comprehensive revision is getting underway. It, too, is likely to drop SIRS into the wastebasket, Dr. Schlapbach said.
“It is probably time to abandon the old view of sepsis disease progression, which proposes a progression from infection to SIRS to severe sepsis with organ dysfunction to septic shock, because most children with infection do manifest signs of SIRS, such as tachycardia, tachypnea, and fever, and these probably should be considered as more of an adaptive rather than a maladaptive response,” he explained.
The goal of the pediatric sepsis redefinition project is to come up with something more useful for clinicians than the Sepsis-3 definition. While the Sepsis-3 concept of a dysregulated host response to infection sounds nice, he explained, “we don’t actually know what it is.
“One of the challenges that you all know as pediatricians is that children who develop sepsis get sick very, very quickly. We all have memories of children who we saw and may have discharged, and they were dead 12 hours later,” he noted.
Indeed, he and others have shown in multiple studies that up to 50% of pediatric deaths caused by sepsis happen within 24 hours of presentation.
“So whatever happens, it happens very quickly. The true question for us is actually how and why do children progress from no organ dysfunction, where the mortality is close to zero, to organ dysfunction, where all of a sudden mortality jumps up dramatically. It’s this progression that we don’t understand at all,” according to Dr. Schlapbach.
The genetic contribution to fulminant sepsis in children may be substantial
One-third of pediatric sepsis deaths in high-income countries happen in previously healthy children. In a proof-of-concept study, Dr. Schlapbach and coinvestigators in the Swiss Pediatric Sepsis Study Group conducted exome-sequencing genetic studies in eight previously healthy children with no family history of immunodeficiency who died of severe sepsis because of community-acquired Pseudomonas aeruginosa infection. Two of the eight had rare loss-of-function mutations in genes known to cause primary immunodeficiencies. The investigators proposed that unusually severe sepsis in previously healthy children warrants exome sequencing to look for underlying previously undetected primary immunodeficiencies. That’s important information for survivors and/or affected families to have, they argued (Front Immunol. 2016 Sep 20;7:357. eCollection 2016).
“There are some indications that the genetic contribution in children with sepsis may be larger than previously assumed,” he said.
The longstanding practice of fluid bolus therapy for resuscitation in pediatric sepsis is being reexamined
The FEAST (Fluid Expansion As Supportive Therapy) study, a randomized trial of more than 3,000 children with severe febrile illness and impaired perfusion in sub-Saharan Africa, turned heads with its finding that fluid boluses significantly increased 48-hour mortality (BMC Med. 2013 Mar 14;11:67).
Indeed, the FEAST findings, supported by mechanistic animal studies, were sufficiently compelling that the use of fluid boluses in both pediatric and adult septic shock is now under scrutiny in two major randomized trials: RIFTS (the Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock), and CLOVERS (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis). Stay tuned.
Dr. Schlapbach reported having no financial conflicts regarding his presentation.
LJUBLJANA, SLOVENIA – The dogma of the “Golden Hour” for the immediate management of pediatric sepsis has been oversold and actually is based upon weak evidence, Luregn J. Schlapbach, MD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.
The true Golden Hour – that is, the time frame within which it’s imperative to administer the sepsis bundle comprised of appropriate antibiotics, fluids, and inotropes – is probably more like 3 hours.
“The evidence suggests that up to 3 hours you don’t really have a big difference in outcomes for sepsis. If you recognize shock there’s no question: You should not even wait 1 hour. But if you’re not certain, it may be better to give up to 3 hours to work up the child and get the senior clinician involved before you make decisions about treatment. So I’m not advocating to delay anything, said Dr. Schlapbach, a pediatric intensivist at the Child Health Research Center at the University of Queensland in South Brisbane, Australia.
The problem with a 1-hour mandate for delivery of the sepsis bundle, as recommended in guidelines by the Surviving Sepsis Campaign and the American College of Critical Care Medicine, and endorsed in quality improvement initiatives, is that the time pressure pushes physicians to overprescribe antibiotics to children who don’t actually have a serious bacterial infection. And that, he noted, contributes to the growing problem of antimicrobial resistance.
“You may have a child where you’re not too sure. Usually you would have done a urine culture because UTI [urinary tract infection] is quite a common cause of these infections, and many of these kids aren’t necessarily septic. But if people tell you that within 1 hour you need to treat, are you going to take the time to do the urine culture, or are you just going to decide to treat?” he asked rhetorically.
Dr. Schlapbach is a world-renowned pediatric sepsis researcher. He is far from alone in his reservations about the Golden Hour mandate.
“This is one of the reasons why IDSA [the Infectious Diseases Society of America] has not endorsed the Surviving Sepsis Campaign,” according to the physician, who noted that, in a position statement, IDSA officials have declared that discrimination of sepsis from noninfectious conditions remains a challenge, and that a 60-minute time to antibiotics may jeopardize patient reassessment (Clin Infect Dis. 2018 May 15;66[10]:1631-5).
Dr. Schlapbach highlighted other recent developments in pediatric sepsis.
The definition of adult sepsis has changed, and the pediatric version needs to as well
The revised definition of sepsis, known as Sepsis-3, issued by the International Sepsis Definition Task Force in 2016 notably dropped systemic inflammatory response syndrome (SIRS), as a requirement for sepsis (JAMA. 2016;315[8]:801-10). The revised definition characterizes sepsis as a dysregulated host response to infection resulting in life-threatening organ dysfunction. But Sepsis-3 is based entirely on adult data and is not considered applicable to children.
The current Pediatric Sepsis Consensus Conference definition dates back to 2005. A comprehensive revision is getting underway. It, too, is likely to drop SIRS into the wastebasket, Dr. Schlapbach said.
“It is probably time to abandon the old view of sepsis disease progression, which proposes a progression from infection to SIRS to severe sepsis with organ dysfunction to septic shock, because most children with infection do manifest signs of SIRS, such as tachycardia, tachypnea, and fever, and these probably should be considered as more of an adaptive rather than a maladaptive response,” he explained.
The goal of the pediatric sepsis redefinition project is to come up with something more useful for clinicians than the Sepsis-3 definition. While the Sepsis-3 concept of a dysregulated host response to infection sounds nice, he explained, “we don’t actually know what it is.
“One of the challenges that you all know as pediatricians is that children who develop sepsis get sick very, very quickly. We all have memories of children who we saw and may have discharged, and they were dead 12 hours later,” he noted.
Indeed, he and others have shown in multiple studies that up to 50% of pediatric deaths caused by sepsis happen within 24 hours of presentation.
“So whatever happens, it happens very quickly. The true question for us is actually how and why do children progress from no organ dysfunction, where the mortality is close to zero, to organ dysfunction, where all of a sudden mortality jumps up dramatically. It’s this progression that we don’t understand at all,” according to Dr. Schlapbach.
The genetic contribution to fulminant sepsis in children may be substantial
One-third of pediatric sepsis deaths in high-income countries happen in previously healthy children. In a proof-of-concept study, Dr. Schlapbach and coinvestigators in the Swiss Pediatric Sepsis Study Group conducted exome-sequencing genetic studies in eight previously healthy children with no family history of immunodeficiency who died of severe sepsis because of community-acquired Pseudomonas aeruginosa infection. Two of the eight had rare loss-of-function mutations in genes known to cause primary immunodeficiencies. The investigators proposed that unusually severe sepsis in previously healthy children warrants exome sequencing to look for underlying previously undetected primary immunodeficiencies. That’s important information for survivors and/or affected families to have, they argued (Front Immunol. 2016 Sep 20;7:357. eCollection 2016).
“There are some indications that the genetic contribution in children with sepsis may be larger than previously assumed,” he said.
The longstanding practice of fluid bolus therapy for resuscitation in pediatric sepsis is being reexamined
The FEAST (Fluid Expansion As Supportive Therapy) study, a randomized trial of more than 3,000 children with severe febrile illness and impaired perfusion in sub-Saharan Africa, turned heads with its finding that fluid boluses significantly increased 48-hour mortality (BMC Med. 2013 Mar 14;11:67).
Indeed, the FEAST findings, supported by mechanistic animal studies, were sufficiently compelling that the use of fluid boluses in both pediatric and adult septic shock is now under scrutiny in two major randomized trials: RIFTS (the Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock), and CLOVERS (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis). Stay tuned.
Dr. Schlapbach reported having no financial conflicts regarding his presentation.
LJUBLJANA, SLOVENIA – The dogma of the “Golden Hour” for the immediate management of pediatric sepsis has been oversold and actually is based upon weak evidence, Luregn J. Schlapbach, MD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.
The true Golden Hour – that is, the time frame within which it’s imperative to administer the sepsis bundle comprised of appropriate antibiotics, fluids, and inotropes – is probably more like 3 hours.
“The evidence suggests that up to 3 hours you don’t really have a big difference in outcomes for sepsis. If you recognize shock there’s no question: You should not even wait 1 hour. But if you’re not certain, it may be better to give up to 3 hours to work up the child and get the senior clinician involved before you make decisions about treatment. So I’m not advocating to delay anything, said Dr. Schlapbach, a pediatric intensivist at the Child Health Research Center at the University of Queensland in South Brisbane, Australia.
The problem with a 1-hour mandate for delivery of the sepsis bundle, as recommended in guidelines by the Surviving Sepsis Campaign and the American College of Critical Care Medicine, and endorsed in quality improvement initiatives, is that the time pressure pushes physicians to overprescribe antibiotics to children who don’t actually have a serious bacterial infection. And that, he noted, contributes to the growing problem of antimicrobial resistance.
“You may have a child where you’re not too sure. Usually you would have done a urine culture because UTI [urinary tract infection] is quite a common cause of these infections, and many of these kids aren’t necessarily septic. But if people tell you that within 1 hour you need to treat, are you going to take the time to do the urine culture, or are you just going to decide to treat?” he asked rhetorically.
Dr. Schlapbach is a world-renowned pediatric sepsis researcher. He is far from alone in his reservations about the Golden Hour mandate.
“This is one of the reasons why IDSA [the Infectious Diseases Society of America] has not endorsed the Surviving Sepsis Campaign,” according to the physician, who noted that, in a position statement, IDSA officials have declared that discrimination of sepsis from noninfectious conditions remains a challenge, and that a 60-minute time to antibiotics may jeopardize patient reassessment (Clin Infect Dis. 2018 May 15;66[10]:1631-5).
Dr. Schlapbach highlighted other recent developments in pediatric sepsis.
The definition of adult sepsis has changed, and the pediatric version needs to as well
The revised definition of sepsis, known as Sepsis-3, issued by the International Sepsis Definition Task Force in 2016 notably dropped systemic inflammatory response syndrome (SIRS), as a requirement for sepsis (JAMA. 2016;315[8]:801-10). The revised definition characterizes sepsis as a dysregulated host response to infection resulting in life-threatening organ dysfunction. But Sepsis-3 is based entirely on adult data and is not considered applicable to children.
The current Pediatric Sepsis Consensus Conference definition dates back to 2005. A comprehensive revision is getting underway. It, too, is likely to drop SIRS into the wastebasket, Dr. Schlapbach said.
“It is probably time to abandon the old view of sepsis disease progression, which proposes a progression from infection to SIRS to severe sepsis with organ dysfunction to septic shock, because most children with infection do manifest signs of SIRS, such as tachycardia, tachypnea, and fever, and these probably should be considered as more of an adaptive rather than a maladaptive response,” he explained.
The goal of the pediatric sepsis redefinition project is to come up with something more useful for clinicians than the Sepsis-3 definition. While the Sepsis-3 concept of a dysregulated host response to infection sounds nice, he explained, “we don’t actually know what it is.
“One of the challenges that you all know as pediatricians is that children who develop sepsis get sick very, very quickly. We all have memories of children who we saw and may have discharged, and they were dead 12 hours later,” he noted.
Indeed, he and others have shown in multiple studies that up to 50% of pediatric deaths caused by sepsis happen within 24 hours of presentation.
“So whatever happens, it happens very quickly. The true question for us is actually how and why do children progress from no organ dysfunction, where the mortality is close to zero, to organ dysfunction, where all of a sudden mortality jumps up dramatically. It’s this progression that we don’t understand at all,” according to Dr. Schlapbach.
The genetic contribution to fulminant sepsis in children may be substantial
One-third of pediatric sepsis deaths in high-income countries happen in previously healthy children. In a proof-of-concept study, Dr. Schlapbach and coinvestigators in the Swiss Pediatric Sepsis Study Group conducted exome-sequencing genetic studies in eight previously healthy children with no family history of immunodeficiency who died of severe sepsis because of community-acquired Pseudomonas aeruginosa infection. Two of the eight had rare loss-of-function mutations in genes known to cause primary immunodeficiencies. The investigators proposed that unusually severe sepsis in previously healthy children warrants exome sequencing to look for underlying previously undetected primary immunodeficiencies. That’s important information for survivors and/or affected families to have, they argued (Front Immunol. 2016 Sep 20;7:357. eCollection 2016).
“There are some indications that the genetic contribution in children with sepsis may be larger than previously assumed,” he said.
The longstanding practice of fluid bolus therapy for resuscitation in pediatric sepsis is being reexamined
The FEAST (Fluid Expansion As Supportive Therapy) study, a randomized trial of more than 3,000 children with severe febrile illness and impaired perfusion in sub-Saharan Africa, turned heads with its finding that fluid boluses significantly increased 48-hour mortality (BMC Med. 2013 Mar 14;11:67).
Indeed, the FEAST findings, supported by mechanistic animal studies, were sufficiently compelling that the use of fluid boluses in both pediatric and adult septic shock is now under scrutiny in two major randomized trials: RIFTS (the Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock), and CLOVERS (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis). Stay tuned.
Dr. Schlapbach reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM ESPID 2019