SCCM Resource Library-35-Impact of Timing of Acute Neurologic Dysfunction on Outcomes in Pediatric Sepsis

Video Transcription

Hello, I want to thank the Congress Committee for this opportunity. My name is Alicia Alcamo, and I am an assistant professor at the Children's Hospital of Philadelphia.  I will be presenting this work today on behalf of the Sprout Study investigators and policy. My work is entitled The Impact of Timing of Acute Neurologic Dysfunction on Outcomes  in Pediatric Sepsis. We have no disclosures. Clinically, when acute neurologic dysfunction occurs in sepsis, the presentation of this dysfunction occurs along a spectrum.  Patients may experience transient symptoms, such as confusion or irritability, or may have more persistent symptoms, like encephalopathy.  Based on the initial Sprout Study, approximately 15% of pediatric sepsis patients experience neurologic dysfunction in sepsis.  The presence of acute neurologic dysfunction in septic adults is associated with up to a two-fold increased odds of mortality.  In a cohort of pediatric sepsis patients who died, over half had neurological dysfunction at the time of death, and 20% had neurologic injury listed as a cause of death.  In a previous secondary analysis of the Sprout Study, patients who developed neurologic dysfunction  during the first week of sepsis had a 4.6-fold increased odds of death compared to patients who did not experience neurologic dysfunction.  Our question was whether there was a difference in mortality and moderate functional disability based on the timing of onset of neurologic dysfunction in sepsis.  Our study aim was to determine if the timing of acute neurologic dysfunction onset was associated with worse outcomes.  Our hypothesis was that for patients who experienced neurologic dysfunction after day one of sepsis,  or after sepsis onset, would be more likely to die or have moderate functional disability if they survived.  This was a secondary analysis of the Sprout Point Prevalence Study that included data from 128 sites in 26 countries.  Sepsis was classified by the International Pediatric Sepsis Conference criteria. Patients had to have two or more SIRS criteria, along with a confirmed or suspected infection,  and either cardiovascular dysfunction, acute respiratory distress syndrome, or the presence of two or more other organ dysfunctions.  Neurologic dysfunction was conservatively defined by either a GCS score less than 5, or the presence of fixed and dilated pupils.  Neurologic dysfunction was timed to be at sepsis onset if the patient met criteria for neurologic dysfunction on day one of sepsis detection, or after sepsis onset if the patient  met criteria for neurologic dysfunction between days two through seven of sepsis. Our primary outcome was a composite outcome of either death or moderate functional disability  in survivors. Moderate functional disability was characterized by a POPC or PCPC score greater than or equal to 3, with a change of one or more points from the patient's baseline.  The analysis performed in this study included appropriate descriptive statistics based on if the variables were categorical or continuous.  Multivariable logistic regression was used to assess the association of timing of onset  for neurological dysfunction to the outcome of either death or moderate functional disability. In total, there were 567 patients with sepsis or septic shock within the Sprout study.  When these patients were stratified based on the presence of neurologic dysfunction, the majority of patients did not have neurologic dysfunction during their sepsis course.  And as noted earlier, a total of 15% of patients had neurologic dysfunction during their sepsis episode.  With approximately one third of these patients having neurologic dysfunction after sepsis onset, occurring between days two through seven.  To orient you to this table and the tables that will come, the first column shows data for patients without neurologic dysfunction during sepsis.  The second column includes patients who developed neurologic dysfunction at sepsis onset. And the third column is patients who developed neurologic dysfunction after sepsis onset.  The final column contains a p-value for a comparison of all three groups. As shown in this table, there were no differences in regards to age, gender, race, pre-existing  comorbidities, or baseline POPC or PCPC scores in the three groups. This table illustrates illness severity and infection characteristics for the three groups.  Patients who experienced neurologic dysfunction at sepsis onset had higher PIMP3 scores at the time of ICU admission.  In a separate comparison, evaluating the patients with neurologic dysfunction during sepsis,  there remained a significant increase in PIMP3 score for patients who had neurologic dysfunction  at sepsis onset compared to the patients who developed neurologic dysfunction after sepsis onset. This is demonstrated by the second p-value in the first row.  CNS infections were more common in patients who had neurologic dysfunction during sepsis.  16% of patients with neurologic dysfunction at sepsis onset and 8% of patients with neurologic dysfunction after sepsis onset had a primary CNS infection.  This compared to only 3% of patients who had no neurologic dysfunction during sepsis. There was no difference between the groups based on timing of onset of neurologic dysfunction.  And finally, roughly one third of all infections had a bacterial isolate for all three groups.  Evaluating the number of non-neurologic organ dysfunction at the time of sepsis onset, there was no statistical difference between the three groups.  However, there was a trend for increased number of organ dysfunctions in the patients with neurologic dysfunction at sepsis onset.  Almost all the patients had dysfunction of one or more organs. This table looks at our outcomes.  In the first row, our primary outcome, the composite of mortality and moderate functional disability in survivors.  As you can see, over two thirds of the patients experienced death or moderate functional disability  if neurologic dysfunction was present during sepsis, and this compared to only one third of patients without neurologic dysfunction.  In evaluating the two groups of patients with neurologic dysfunction, there was no difference  in the composite outcome based on the timing of this dysfunction as indicated by the second P value.  And looking at mortality, 20% of patients without neurologic dysfunction died during the study.  However, the mortality rate was significantly higher for patients who experienced neurologic  dysfunction at some point during sepsis with over half of these patients experiencing death.  There was no statistical difference between the groups based on timing of neurologic dysfunction.  Finally, the last row demonstrates the presence of moderate disability in survivors. Only 16% of patients without neurologic dysfunction in sepsis experienced moderate disability.  However, this was significantly increased for patients with neurologic dysfunction during sepsis.  Again, there was no statistical difference between the groups when it came to timing of sepsis onset.  This figure displays the unadjusted odds for our primary outcome of death or moderate functional disability based on timing of neurologic dysfunction onset.  The red line shows the reference odds ratio of one. When compared to patients without neurologic dysfunction during sepsis, patients who developed  neurologic dysfunction at the time of sepsis onset had a 5.5 increased odds of death or moderate functional disability.  And those who developed neurologic dysfunction after sepsis onset had an eightfold increased odds of death or moderate disability.  When we controlled for non-neurologic organ dysfunction at sepsis onset, the presence of CNS infection, and PIM-3 score on ICU admission, patients who had neurologic dysfunction at  sepsis onset had a 3.5 fold increased odds of death or moderate functional disability, while those with neurologic dysfunction after sepsis onset had a ninefold increased odds  of death or moderate functional disability. Again, this was compared to patients without neurologic dysfunction.  However, the odds for a poor outcome were not different based on timing of onset of neurologic dysfunction.  In this figure, we are demonstrating the presence of poor outcomes based on the timing of neurologic dysfunction onset.  Death or moderate disability is shown in red, while survival without moderate functional disability is shown in blue.  As you can see, there appears to be a trend for worsening outcomes based on timing of neurologic dysfunction onset.  Over 60% of patients with onset of neurological dysfunction on day one of sepsis experienced death or moderate functional disability, while 100% of patients who developed neurologic  dysfunction on day six or seven died and had moderate disability. Given our small sample size, further analyses to assess this relationship of timing is not  feasible in this data set. There are several limitations in our analysis. First, there was an overall small sample size of children who experienced neurologic dysfunction  during sepsis, which, as previously noted, limited additional analyses to assess associations between timing of neurological onset and outcomes.  In addition, the definition used to define neurological dysfunction during sepsis was conservative and may have missed transient or milder presentations of neurologic dysfunction.  Lastly, data was not collected regarding medication exposures. Many medications may impact GCS scoring during the observation period and, therefore, the  detection of neurologic dysfunction. In conclusion, acute neurologic dysfunction in pediatric sepsis is associated with death and functional disability.  Our data suggests that there might be a higher risk of poor outcomes if neurologic dysfunction  occurs after sepsis onset, but further studies are needed to understand the impact of timing for neurological dysfunction and outcomes.  I would like to thank everyone in this photo who has helped with the secondary analysis, as well as the other Sprout investigators who were involved with creation of this data set.  I am happy to take any questions, and I have included my email for further communication on this slide. ♪♪♪

Video Summary

Alicia Alcamo, an assistant professor at the Children's Hospital of Philadelphia, presents her work on the impact of the timing of acute neurologic dysfunction on outcomes in pediatric sepsis. The study found that neurologic dysfunction in septic children is associated with a higher risk of death and functional disability. The analysis showed that patients who developed neurologic dysfunction at the time of sepsis onset had a 3.5-fold increased odds of death or moderate disability, while those who developed neurologic dysfunction after sepsis onset had a 9-fold increased odds. However, further research is needed to fully understand the impact of timing on outcomes.

Asset Subtitle

Pediatrics, Sepsis, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Alicia M. Alcamo

Introduction/Hypothesis: Acute neurological dysfunction (ND) in sepsis is associated with risk for poor outcomes but whether the timing of ND onset during sepsis differentially affects this risk is unknown. We hypothesized that children who developed ND after sepsis onset have higher risk of poor outcomes compared to ND at sepsis onset.

Methods: We performed a retrospective study using the SPROUT pediatric sepsis data from 128 sites in 26 countries. ND defined using Proulx criteria (GCS<5 or fixed/dilated pupils). Timing of acute ND was categorized as 1) ND at sepsis onset (day 1), 2) ND after sepsis onset (days 2-7), or 3) no ND. We compared categorical data with Fischer's exact and continuous data with Kruskal-Wallis tests. We used logistic regression to test the association of timing of ND with death or functional disability (worsening POPC/PCPC scores) at hospital discharge.

Results: Among 567 children with sepsis/septic shock, 61 (10.8%) had ND at sepsis onset, 26 (4.6%) had ND after sepsis onset, and 480 (84.6%) had no ND. Age, sex, race, comorbidities, baseline POPC/PCPC scores did not differ between groups (all p>0.05). Median (IQR) PIM3 score was higher in ND at sepsis onset than ND after onset and no ND (14.6 [4.6-25.4] vs 6.2 [4.3-11.1] vs 4.0 [1.8-7.9], p<0.001). CNS infection was more common with ND at sepsis onset than after onset and no ND (16% vs 8% vs 3%, p<0.001). Dysfunction of three or more organs on sepsis presentation was more common in ND at sepsis onset (64%) than ND after sepsis onset (27%) or no ND (22%, p<0.001). Death or functional disability occurred in 74% with ND at sepsis onset, 81% with ND after sepsis onset, and 34% with no ND (p<0.001 between all groups, p=0.59 between ND at vs after sepsis). After controlling for PIM3, CNS infection, and â‰¥3 organ dysfunction at sepsis presentation, patients with ND at sepsis onset (aOR 2.6, 95%CI 1.3-5.2) and ND after sepsis onset (aOR 8.1, 95%CI 3.0-22.3) had increased death/functional disability compared with no ND (both p<0.01), but the odds were not different by timing of ND (p=0.06).

Conclusions: Children with acute ND during sepsis have a higher rate of death or functional disability at hospital discharge than those with no ND during sepsis, with a suggestion of higher risk of poor outcomes if ND occurred after as compared to at sepsis onset.

Meta Tag

Content Type Presentation

Knowledge Area Pediatrics

Knowledge Area Sepsis

Knowledge Level Advanced

Membership Level Select

Tag Monitoring

Tag Scoring Systems

Year 2021

Keywords

Alicia Alcamo

assistant professor

Children's Hospital of Philadelphia

neurologic dysfunction

pediatric sepsis

	Society of Critical Care Medicine 500 Midway Drive Mount Prospect, IL 60056 USA Phone: +1 847 827-6888 Fax: +1 847 439-7226 Email: support@sccm.org	Contact Us About SCCM Newsroom Advertising & Sponsorship DONATE	MySCCM LearnICU Patients & Families Surviving Sepsis Campaign Critical Care Societies Collaborative	GET OUR NEWSLETTER
© Society of Critical Care Medicine. All rights reserved. \| Privacy Statement \| Terms & Conditions The Society of Critical Care Medicine, SCCM, and Critical Care Congress are registered trademarks of the Society of Critical Care Medicine.