SCCM Resource Library-Autonomic Nervous System Dysfunction is Associated with Rehospitalization in Pediatric Septic Shock

Video Transcription

Hi, my name is Colleen Badke. I'm from Lurie Children's Hospital in Chicago, and I'd like to thank you all for joining  my talk today, where I will be discussing autonomic nervous system dysfunction and its association with re-hospitalization in pediatric septic shock survivors.  Sepsis is common in the pediatric critically ill child, and it's associated with significant morbidity and mortality.  Additionally, up to 35% of survivors of pediatric septic shock go on to develop deterioration in their health-related quality of life, up to a year following their hospitalization.  Children who experience sepsis and septic shock are more likely to utilize the healthcare system subsequent to that diagnosis.  There are many factors that are associated with sepsis that may increase the child's risk for death or deterioration in their health-related quality of life.  These include certain therapies while they are admitted for septic shock, such as renal replacement therapy, ECMO, and CPR, as well as certain comorbidities, such as oncologic,  hematologic, immunologic, and neurologic comorbidities. All of these place patients at higher risk of readmission to the hospital following their initial septic shock admission.  We also know that children less than one year of age and those with certain infections, such as bloodstream infections, cardiovascular infections, or GU infections, are at higher  risk for readmission. Different measures of the autonomic nervous system have been used to risk-stratify critically ill children who are at risk for poor outcomes.  However, it's unknown if measuring the autonomic nervous system may be predictive of which children are at risk for readmission following sepsis.  The autonomic nervous system is unique in that it regulates functions in nearly every organ system, and it attempts to maintain homeostasis within all organ systems.  However, what we see in sepsis, as well as other critical illness, is an imbalance between the sympathetic and parasympathetic branches of the autonomic nervous system, specifically  an excessive or uncontrolled sympathetic surge. This imbalance leads to dysfunction within the autonomic nervous system, and clinically  we can measure this at the bedside or in research studies using heart rate variability, which is a non-invasive, continuous physiologic marker of autonomic nervous system function.  We know that heart rate variability in both children and adults is predictive of in-hospital mortality, as well as certain outcomes, such as organ failure.  So the objective of this study was to assess whether heart rate variability during admission for pediatric septic shock is associated with re-hospitalization in those children  within a year. This was a retrospective observational cohort study from 2012 to 2020 at a single institution.  We looked at patients who were admitted to our PICU with septic shock and who had continuous heart rate data available from the bedside monitor.  We defined septic shock as children who needed vasoactive infusions within 72 hours of PICU admission who also had a confirmed or suspected infection.  Using the continuous bedside monitor data, we calculated the integer heart rate variability. We did this by taking the heart rate, which is measured and recorded every one second,  and then taking the standard deviation of those heart rates over five minutes. This was the HRVI, or integer heart rate variability.  Since heart rate and heart rate variability vary with age, we then calculated age-normalized HRVI values.  And we did this by using the final 24 hours of PICU stay for survivors as a proxy for homeostasis within the population.  We used that 24-hour period as a reference to calculate the median normalized HRVI measurements.  We then calculated 24-hour median HRVI measurements on two separate days during the index PICU admission.  We looked at the last 24 hours of PICU stay and calculated the median HRVI during that period. And then we also identified the lowest HRVI measurement during the PICU admission and  calculated the 24-hour median of HRVI values during that period. The change between the lowest and the last HRVI was also calculated and termed the delta HRVI.  Our primary outcome was all-cause re-hospitalization to our institution within one year, and this  included emergency department visits as well as readmission to the hospital, either the inpatient or the ICU environment.  Our secondary outcome was the total number of re-hospitalizations, which included inpatient or ICU, within one year from the index admission to our institution.  To determine if there were differences in the associations based on the timeframe of re-hospitalization, we also performed a sensitivity analysis that looked at re-hospitalization  at 30 days and at 90 days from the index admission. We analyzed our data in R, performed Kruskal-Wallis and Chi-squared tests, logistic regression  for the primary outcome, and Poisson regression for the secondary outcome. Finally, to address possible confounders of re-hospitalization, we used a multivariable  regression analysis to adjust for age, severity of illness using PRISM-3, immunocompromised state, and chronic comorbid conditions.  There were 463 patients who met inclusion criteria during our study period. Of those patients, 306, or 66%, were re-hospitalized within one year, and 270 of those patients  were readmitted to either an inpatient ward or an ICU. Patients who were re-hospitalized were more likely to be non-white and Hispanic-Latino  and more likely to be immunocompromised. Patients with more comorbidities were also more likely to be re-hospitalized.  We saw no differences in sex, age, PRISM-3 score, technology dependence, length of stay, or ventilator-free days or inotrope-free days in readmission.  This table shows our three 24-hour median HRVI measurements for the septic shock survivors. The median last HRVI measurement during the index admission was significantly lower among  patients who were re-hospitalized compared to those who were not re-hospitalized. The median lowest HRVI measurement was not significantly different between patients who  were re-hospitalized and those who were not. Patients who were re-hospitalized showed a smaller improvement in their delta HRVI from the lowest to the last HRVI measurement.  In our sensitivity analysis, looking at 30- and 90-day readmissions, the delta HRVI remained  significantly associated with re-hospitalization with a higher value associated with a lower likelihood of readmission.  This table shows the unadjusted and adjusted odds ratios for re-hospitalization after septic shock admission based on the age-normalized HRVI measurements.  After controlling for potential confounders, which included age, PRISM-3 or severity of  illness, immunocompromised state, and comorbidities, we found that the median last as well as the  delta HRVI measurements remained significantly associated with re-hospitalization with higher HRVI measurements associated with a lower odds of re-hospitalization.  Our secondary outcome was to examine the total number of re-hospitalizations and its association with HRVI measurements.  Patients who were re-hospitalized in our cohort had on average three re-hospitalizations with an interquartile range of one to six.  And of all the patients who were re-hospitalized, about a third of them were re-hospitalized within 30 days of the index admission and two-thirds re-hospitalized within 90 days.  Similar to our prior results, we found that the median last HRVI and the delta HRVI measurements were significantly associated with the total number of re-hospitalizations.  And this held true after adjusting for age, PRISM-3 or severity of illness, immunocompromised state, and multi-comorbidity.  This meant that higher HRVI measurements were associated with a lower adjusted incidence rate ratio of re-hospitalization. I would like to highlight some limitations of our study.  This was a single-standard study. However, we do present data on a relatively large cohort of septic shock survivors who  had high-frequency physiologic bedside monitor data available during their admission. Our re-hospitalizations only included those to our institution, so we may have missed  re-hospitalizations to other institutions. Next, the way that we estimated heart rate variability was using the integer HRV that I mentioned previously.  This is a more lightweight implementation of HRV and may be more generalizable to institutions who can't perform more complex analysis of heart rate variability.  However, it may not fully capture the physiologic complexity of the autonomic nervous system.  In our cohort, we were unable to account for medications or certain conditions that might affect autonomic nervous system function, so that's another limitation to consider.  And then finally, there may have been some bedside monitor data losses in our cohort. However, these would have occurred at random, and so we don't think this would represent  systematic bias in our cohort. Our retrospective study showed that HRVI is associated with re-hospitalization in pediatric septic shock survivors.  And the big question is, how can we integrate HRVI into prediction tools for children who have septic shock?  To summarize a little further, we looked at three measurements of HRVI during the hospitalization,  the 24-hour period with the lowest HRVI, the 24-hour period prior to discharge, and the delta between those two measurements.  And specifically, we found that the measurement with the strongest association with re-hospitalization  was that delta HRVI, or the measurement that looked at the trajectory of change from the  lowest HRVI measurement, likely when the patient is sickest, to the highest or best measurement on discharge from the PICU, hopefully when the patient is in their most well state.  The delta HRVI association with re-hospitalization was significant at one year, as well as for  30- and 90-day re-hospitalizations, and it also remained significant after we controlled for multiple confounders.  Based on our results, there are a lot of exciting areas of research that we might consider for the future.  One is, how might we be able to incorporate measures such as HRVI into prediction models that might be able to identify which patients are at highest risk for re-hospitalization  after pediatric septic shock? This would be a real-time tool that we could use at the bedside to identify these patients.  And if we are able to identify which patients are at highest risk, then might we be able  to implement different interventions, either during the PICU hospitalization or after discharge, to help mitigate the risk of re-hospitalization in this high-risk cohort?  Another interesting area to consider is if wearable technology, which uses similar lightweight implementations of heart rate, might be able to be used to help predict which patients  at home are deteriorating and at high risk for re-hospitalization. I'd like to thank my research team for all of their contributions with this research  project and the many others that we've worked on together, and I would be happy to take any questions. Thank you so much!

Video Summary

In this talk, Colleen Badke from Lurie Children's Hospital in Chicago discusses autonomic nervous system dysfunction in pediatric septic shock survivors and its association with re-hospitalization. Sepsis is a common and serious condition in critically ill children, and survivors often experience a deterioration in their quality of life after discharge. The autonomic nervous system plays a crucial role in regulating bodily functions, but in sepsis, an imbalance between its branches can occur. Badke's study analyzed heart rate variability as a marker of autonomic nervous system function and found that lower heart rate variability was associated with an increased risk of re-hospitalization. This research suggests potential future interventions to reduce re-hospitalization risk in this high-risk group.

Asset Subtitle

Sepsis, Pediatrics, 2022

Asset Caption

INTRODUCTION: Re-hospitalization after septic shock can lead to impaired quality of life. Predictors of re-hospitalization may identify sepsis survivors at high-risk for re-hospitalization. Our goal was to determine whether low heart rate variability (HRV), a measure of autonomic nervous system dysfunction, is associated with re-hospitalization in pediatric septic shock survivors. METHODS: This was a retrospective, observational cohort study of patients admitted to a single pediatric intensive care unit (PICU) between 2012-2020. Patients with septic shock who had continuous heart rate data available from bedside monitors and survived their hospitalization were included. HRV was measured using the age-adjusted integer HRV (HRVi), which is the standard deviation of the heart rate sampled every 1 second over 5 consecutive minutes and age-normalized. The median HRVi in 24 hours was assessed on two different days: the last 24 hours of PICU admission (“last HRVi”) and the 24-hour period with the lowest median HRVi (“lowest HRVi”). The change between the lowest and last HRVi was calculated (“delta HRVi”). The primary outcome was re-hospitalization to the same institution within 365 days of discharge, including both emergency department encounters and hospital readmission. Kruskal-Wallis tests, logistic regression, and Poisson regression were performed. RESULTS: 463 patients met inclusion criteria. 306 (66%) were re-hospitalized, including 270 readmissions (58%). The median last HRVi was significantly lower among re-hospitalized patients compared to those who were not (-0.35, interquartile range [IQR] -0.63-0.01 vs. -0.22, IQR -0.52-0.06, p = 0.016). There was no difference in the lowest HRVi. Re-hospitalized patients showed a smaller improvement in delta HRVi compared to those who were not (0.44, IQR 0.13-0.84 vs. 0.58, IQR 0.22-1.03, p = 0.024). This association remained significant after adjusting for age, severity of illness using PRISM III, immunocompromised state, and technology dependence. CONCLUSIONS: Lower discharge HRV and a smaller improvement in HRV during admission are significantly associated with re-hospitalization in survivors of pediatric septic shock. This continuous physiologic measure could potentially be used as a predictor of patients at risk for re-hospitalization and lower quality of life.

Meta Tag

Content Type Presentation

Knowledge Area Sepsis

Knowledge Area Pediatrics

Knowledge Level Advanced

Membership Level Select

Tag Shock

Tag Pediatrics

Tag Hemodynamic Monitoring

Year 2022

Keywords

autonomic nervous system dysfunction

pediatric septic shock survivors

re-hospitalization

sepsis

heart rate variability

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