HHS Public Access Author manuscript Author Manuscript
Pediatr Crit Care Med. Author manuscript; available in PMC 2017 May 01. Published in final edited form as: Pediatr Crit Care Med. 2016 May ; 17(5): 444–450. doi:10.1097/PCC.0000000000000709.
Intracranial Hypertension and Cerebral Hypoperfusion in Children with Severe Traumatic Brain Injury: Thresholds and Burden in Accidental and Abusive Insults
Author Manuscript
Nikki Miller Ferguson, MD1,4, Steven L. Shein, MD1,4, Patrick M. Kochanek, MD1,4, Jim Luther3, Stephen R. Wisniewski, PhD3, Robert S. B. Clark, MD1,4, Elizabeth C. Tyler-Kabara, MD2, P. David Adelson, MD5, and Michael J. Bell, MD1,2,4 1Department
of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
2Department
of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
3Department
of Epidemiology and Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, PA
4Safar
Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh,
PA 5Barrow
Neurological Institute at Phoenix Children’s Hospital, Phoenix AZ
Abstract Author Manuscript
Objective—The evidence to guide therapy in pediatric TBI is lacking, including insight into the ICP/CPP thresholds in abusive head trauma (AHT). We examined ICP/CPP thresholds and indices of ICP and CPP burden in relationship to outcome in severe TBI and in accidental and AHT cohorts. Design—A prospective observational study. Setting—PICU in a tertiary children’s hospital. Patients—Children 20 and CPP20 (C=0.641, 95% confidence interval: 0.523, 0.762) and CPP20 and AHT (OR=5.101, 95% CI: 1.571, 16.563). As the number of hours with ICP>20 increase by 1, the odds of a poor outcome increased by 4.6% (OR=1.046, 95% CI: 1.012, 1.082).
Address Correspondence to: Michael J. Bell, MD, Division of Pediatric Critical Care Medicine, University of Pittsburgh School of Medicine, 400 45th Street and Penn Avenue, Pittsburgh, PA 15201, [email protected], Phone: 412-692-5164, Fax: 412-692-6076.
Ferguson et al.
Page 2
Author Manuscript
Thresholds did not differ between accidental vs. AHT. The intracranial hypertension and cerebral hypoperfusion indices were both associated with outcome. Conclusion—The duration of hours of ICP>20 and CPP20 increase by 1, the odds of a poor outcome increased by 4.6%. Although AHT was strongly associated with unfavorable outcome, ICP/CPP thresholds did not differ between accidental and AHT. Keywords traumatic brain injury; cerebral perfusion pressure; intracranial hypertension; intracranial pressure; children; pediatric neurocritical care
Introduction Author Manuscript
Injuries are the leading cause of death in children, with traumatic brain injury (TBI) accounting for the majority of these events (1). According to the Centers for Disease Control and Prevention, there were ~7440 deaths of children $1 billion in inpatient hospital costs. (4) Unfortunately therapies that have been shown to improve outcome in TBI are lacking despite the significant burden it poses. Moreover, abusive head trauma (AHT) is a unique problem in the field of pediatric TBI and has emerged as an increasing contributor to TBI cases in children (5).
Author Manuscript
Measurement and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP = mean arterial pressure [MAP] − ICP) have been mainstays of neurocritical care for decades. Evidenced-based guidelines for the management of severe TBI for both adult and pediatric patients have recommended ICP/CPP monitoring for severe TBI (defined as Glasgow Coma Scale [GCS] score ≤ 8), as well as suggesting therapeutic targets (6, 7). Specifically, a recommendation based on level 2 evidence was made that an ICP threshold of 15 – 25 mm Hg for adult TBI victims should be considered and a recommendation based on level 3 evidence that a CPP threshold of 50 – 70 mm Hg may be considered. For children, there is substantially less evidence available to generate such guidelines. Nevertheless, level 3 recommendations were made to support an ICP treatment threshold of 20 mm Hg and a CPP threshold greater than 40 mm Hg. Further evidence to support such thresholds is needed as some recent studies have challenged the utility of ICP management (8, 9).
Author Manuscript
Pediatric TBI poses a unique challenge because of the various mechanisms of injury, specifically the unique mechanism of AHT that is not seen in other populations. There are a paucity of data explicitly examining this population and the guidelines make no specific recommendations for therapy for this unique group (6). It has been theorized that as this group is mostly comprised of children 50mm Hg for children ≤ 2 y and > 60 mm Hg for children > 2 y). If CPP decreased below these thresholds as a result of intracranial hypertension (ICP > 20 mm Hg), then therapies to lower ICP, described above, were generally first attempted. On the other hand, if CPP decreased below these thresholds without intracranial hypertension, then maneuvers to raise MAP (fluid resuscitation, vasopressor support or other maneuvers) were generally administered. In some patients, both strategies were required.
Author Manuscript
The data collected for this study included demographics extracted from the medical record, physiologic data taken from hourly recordings entered into the medical record by the bedside nurse, and outcomes determined by clinical staff in follow-up clinic. As many children had both an intraparenchymal ICP monitor and EVD, there were hours with more than one ICP and CPP reading. For those hours, the highest ICP and lowest CPP value were used. The outcome data were determined at 6 months after TBI by using the Glasgow Outcomes Scale (GOS) score which was dichotomized for favorable [1–2] and unfavorable [3–5] outcomes.
Author Manuscript
From this database, the number of hours of ICP above certain thresholds (>14, >20, >30 mm Hg) and CPP below certain thresholds (20 and >30), which were used to define intracranial hypertension. For each threshold the number of hours above the threshold for each person was calculated over the first five days after ICP monitor placement. Analyses were then conducted for each threshold to determine if the number of hours above the threshold was associated with outcome. The evaluation of ICP threshold results are shown in Table 3. The model with the number of hours that the ICP exceeded 20 had the best fit (C=0.641, 95% confidence interval: 0.523, 0.762). The confidence intervals of the three estimates overlap indicating that there is not a significant difference between the three estimates of fit and no one threshold is superior (or inferior). A similar approach was used to investigate thresholds for the hours below a specific CPP. Thresholds of CPP (14 mm Hg performs similarly, which begs the question- should we consider a lower ICP therapeutic target in children? This has certainly been theorized over the years that children may require a lower ICP threshold given their normal lower MAP but has never been shown in prior studies, and a much larger sample from a multicenter initiative would be needed to appropriately test that hypothesis. Chambers and colleagues showed significant differences in mean ICP using the same dichotomized outcome groups as our study, as well as age differences in the mean value of ICP correlating with outcomes, all of which were > 20 mm Hg (15). Adelson et al also found mean ICP was significantly greater in those with poor outcome vs. good outcome (12). However, there is inherent validity in the concept that the
Pediatr Crit Care Med. Author manuscript; available in PMC 2017 May 01.
Ferguson et al.
Page 7
Author Manuscript
duration of intracranial pressure derangement could be more clinically relevant than any arithmetic mean – which was borne out in our data.
Author Manuscript
Mean values of variables can be greatly influenced by a few high values and it has been shown by others that episodic ICP increases do not predict outcome. For example, Grinkeviciute et al showed no statistical difference in peak ICP when looking at 6 month outcomes in pediatric TBI (16). A study reported in adults examined ICP in terms of “dose” (defined by area under the curve of ICP > 20 mm Hg over time) of intracranial hypertension. This dose was associated with poor outcomes at 6 months (17). This method also speaks to the need to further characterize increased ICP as more of a burden of disease rather than isolated episodes of an abnormality. We also found that the intracranial hypertension index was significantly associated with outcome, speaking to the relative importance of ICP burden over episodic measurements. However, characterizing the burden of ICP and use of the intracranial hypertension index is difficult to calculate at the bedside and may not be the most useful tool for either acute prognostication or titration of therapies. It may be more helpful in long term prognostication once the acute critical care period is over.
Author Manuscript
We also found that the duration of derangement of CPP appears to be more significant than overall mean values. Similar to the study by Downard et al, we found that the CPP parameter that best discriminated poor outcome was number of hours spent with CPP < 45 mm Hg (14). Our data examining CPP burden appear to confirm and build on that report. Our data did not identify a continuum but did indicate that although 45 mm Hg performed best, a number of other thresholds performed similarly. Another study in children showed that 70% of their population with an initial CPP < 40 mm Hg had unfavorable outcome (18). Allen et al recently found age related CPP thresholds associated with poor outcome, showing that time spent below specific thresholds was related to decreased survival (19). Adelson et al found that the percent of time with CPP > 50 mm Hg was greater in children with good vs. poor outcome (12). The cerebral hypoperfusion index was significantly associated with outcome. Indeed for both ICP and CPP a personalized threshold may ultimately need to be derived based not only on ICP and CPP values, but additional information such as brain tissue oxygenation, microdialysis monitoring, or pressure reactivity index, as was suggested recently in the work of Weersink et al and Allen et al (19, 20).
Author Manuscript
In addition to exploring the impact of burden of ICP and CPP, another goal was to address the lack of data on infants with severe TBI resulting from AHT in the guidelines; and as to whether or not AHT is a different disease than accidental TBI. Surprisingly, we found no significant differences in the associations between ICP and CPP and outcome in the AHT vs. accidental cohorts. This may in part reflect a somewhat smaller sample size of this population in our study (18 patients). However, in support of our findings, a recent paper analyzing a subset of our cohort of < 2y TBI subjects found a similar lack of association between ICP thresholds and outcome in infants with AHT and only a single CPP threshold, namely, CPP
Pediatr Crit Care Med. Author manuscript; available in PMC 2017 May 01. Published in final edited form as: Pediatr Crit Care Med. 2016 May ; 17(5): 444–450. doi:10.1097/PCC.0000000000000709.
Intracranial Hypertension and Cerebral Hypoperfusion in Children with Severe Traumatic Brain Injury: Thresholds and Burden in Accidental and Abusive Insults
Author Manuscript
Nikki Miller Ferguson, MD1,4, Steven L. Shein, MD1,4, Patrick M. Kochanek, MD1,4, Jim Luther3, Stephen R. Wisniewski, PhD3, Robert S. B. Clark, MD1,4, Elizabeth C. Tyler-Kabara, MD2, P. David Adelson, MD5, and Michael J. Bell, MD1,2,4 1Department
of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
2Department
of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
3Department
of Epidemiology and Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, PA
4Safar
Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh,
PA 5Barrow
Neurological Institute at Phoenix Children’s Hospital, Phoenix AZ
Abstract Author Manuscript
Objective—The evidence to guide therapy in pediatric TBI is lacking, including insight into the ICP/CPP thresholds in abusive head trauma (AHT). We examined ICP/CPP thresholds and indices of ICP and CPP burden in relationship to outcome in severe TBI and in accidental and AHT cohorts. Design—A prospective observational study. Setting—PICU in a tertiary children’s hospital. Patients—Children 20 and CPP20 (C=0.641, 95% confidence interval: 0.523, 0.762) and CPP20 and AHT (OR=5.101, 95% CI: 1.571, 16.563). As the number of hours with ICP>20 increase by 1, the odds of a poor outcome increased by 4.6% (OR=1.046, 95% CI: 1.012, 1.082).
Address Correspondence to: Michael J. Bell, MD, Division of Pediatric Critical Care Medicine, University of Pittsburgh School of Medicine, 400 45th Street and Penn Avenue, Pittsburgh, PA 15201, [email protected], Phone: 412-692-5164, Fax: 412-692-6076.
Ferguson et al.
Page 2
Author Manuscript
Thresholds did not differ between accidental vs. AHT. The intracranial hypertension and cerebral hypoperfusion indices were both associated with outcome. Conclusion—The duration of hours of ICP>20 and CPP20 increase by 1, the odds of a poor outcome increased by 4.6%. Although AHT was strongly associated with unfavorable outcome, ICP/CPP thresholds did not differ between accidental and AHT. Keywords traumatic brain injury; cerebral perfusion pressure; intracranial hypertension; intracranial pressure; children; pediatric neurocritical care
Introduction Author Manuscript
Injuries are the leading cause of death in children, with traumatic brain injury (TBI) accounting for the majority of these events (1). According to the Centers for Disease Control and Prevention, there were ~7440 deaths of children $1 billion in inpatient hospital costs. (4) Unfortunately therapies that have been shown to improve outcome in TBI are lacking despite the significant burden it poses. Moreover, abusive head trauma (AHT) is a unique problem in the field of pediatric TBI and has emerged as an increasing contributor to TBI cases in children (5).
Author Manuscript
Measurement and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP = mean arterial pressure [MAP] − ICP) have been mainstays of neurocritical care for decades. Evidenced-based guidelines for the management of severe TBI for both adult and pediatric patients have recommended ICP/CPP monitoring for severe TBI (defined as Glasgow Coma Scale [GCS] score ≤ 8), as well as suggesting therapeutic targets (6, 7). Specifically, a recommendation based on level 2 evidence was made that an ICP threshold of 15 – 25 mm Hg for adult TBI victims should be considered and a recommendation based on level 3 evidence that a CPP threshold of 50 – 70 mm Hg may be considered. For children, there is substantially less evidence available to generate such guidelines. Nevertheless, level 3 recommendations were made to support an ICP treatment threshold of 20 mm Hg and a CPP threshold greater than 40 mm Hg. Further evidence to support such thresholds is needed as some recent studies have challenged the utility of ICP management (8, 9).
Author Manuscript
Pediatric TBI poses a unique challenge because of the various mechanisms of injury, specifically the unique mechanism of AHT that is not seen in other populations. There are a paucity of data explicitly examining this population and the guidelines make no specific recommendations for therapy for this unique group (6). It has been theorized that as this group is mostly comprised of children 50mm Hg for children ≤ 2 y and > 60 mm Hg for children > 2 y). If CPP decreased below these thresholds as a result of intracranial hypertension (ICP > 20 mm Hg), then therapies to lower ICP, described above, were generally first attempted. On the other hand, if CPP decreased below these thresholds without intracranial hypertension, then maneuvers to raise MAP (fluid resuscitation, vasopressor support or other maneuvers) were generally administered. In some patients, both strategies were required.
Author Manuscript
The data collected for this study included demographics extracted from the medical record, physiologic data taken from hourly recordings entered into the medical record by the bedside nurse, and outcomes determined by clinical staff in follow-up clinic. As many children had both an intraparenchymal ICP monitor and EVD, there were hours with more than one ICP and CPP reading. For those hours, the highest ICP and lowest CPP value were used. The outcome data were determined at 6 months after TBI by using the Glasgow Outcomes Scale (GOS) score which was dichotomized for favorable [1–2] and unfavorable [3–5] outcomes.
Author Manuscript
From this database, the number of hours of ICP above certain thresholds (>14, >20, >30 mm Hg) and CPP below certain thresholds (20 and >30), which were used to define intracranial hypertension. For each threshold the number of hours above the threshold for each person was calculated over the first five days after ICP monitor placement. Analyses were then conducted for each threshold to determine if the number of hours above the threshold was associated with outcome. The evaluation of ICP threshold results are shown in Table 3. The model with the number of hours that the ICP exceeded 20 had the best fit (C=0.641, 95% confidence interval: 0.523, 0.762). The confidence intervals of the three estimates overlap indicating that there is not a significant difference between the three estimates of fit and no one threshold is superior (or inferior). A similar approach was used to investigate thresholds for the hours below a specific CPP. Thresholds of CPP (14 mm Hg performs similarly, which begs the question- should we consider a lower ICP therapeutic target in children? This has certainly been theorized over the years that children may require a lower ICP threshold given their normal lower MAP but has never been shown in prior studies, and a much larger sample from a multicenter initiative would be needed to appropriately test that hypothesis. Chambers and colleagues showed significant differences in mean ICP using the same dichotomized outcome groups as our study, as well as age differences in the mean value of ICP correlating with outcomes, all of which were > 20 mm Hg (15). Adelson et al also found mean ICP was significantly greater in those with poor outcome vs. good outcome (12). However, there is inherent validity in the concept that the
Pediatr Crit Care Med. Author manuscript; available in PMC 2017 May 01.
Ferguson et al.
Page 7
Author Manuscript
duration of intracranial pressure derangement could be more clinically relevant than any arithmetic mean – which was borne out in our data.
Author Manuscript
Mean values of variables can be greatly influenced by a few high values and it has been shown by others that episodic ICP increases do not predict outcome. For example, Grinkeviciute et al showed no statistical difference in peak ICP when looking at 6 month outcomes in pediatric TBI (16). A study reported in adults examined ICP in terms of “dose” (defined by area under the curve of ICP > 20 mm Hg over time) of intracranial hypertension. This dose was associated with poor outcomes at 6 months (17). This method also speaks to the need to further characterize increased ICP as more of a burden of disease rather than isolated episodes of an abnormality. We also found that the intracranial hypertension index was significantly associated with outcome, speaking to the relative importance of ICP burden over episodic measurements. However, characterizing the burden of ICP and use of the intracranial hypertension index is difficult to calculate at the bedside and may not be the most useful tool for either acute prognostication or titration of therapies. It may be more helpful in long term prognostication once the acute critical care period is over.
Author Manuscript
We also found that the duration of derangement of CPP appears to be more significant than overall mean values. Similar to the study by Downard et al, we found that the CPP parameter that best discriminated poor outcome was number of hours spent with CPP < 45 mm Hg (14). Our data examining CPP burden appear to confirm and build on that report. Our data did not identify a continuum but did indicate that although 45 mm Hg performed best, a number of other thresholds performed similarly. Another study in children showed that 70% of their population with an initial CPP < 40 mm Hg had unfavorable outcome (18). Allen et al recently found age related CPP thresholds associated with poor outcome, showing that time spent below specific thresholds was related to decreased survival (19). Adelson et al found that the percent of time with CPP > 50 mm Hg was greater in children with good vs. poor outcome (12). The cerebral hypoperfusion index was significantly associated with outcome. Indeed for both ICP and CPP a personalized threshold may ultimately need to be derived based not only on ICP and CPP values, but additional information such as brain tissue oxygenation, microdialysis monitoring, or pressure reactivity index, as was suggested recently in the work of Weersink et al and Allen et al (19, 20).
Author Manuscript
In addition to exploring the impact of burden of ICP and CPP, another goal was to address the lack of data on infants with severe TBI resulting from AHT in the guidelines; and as to whether or not AHT is a different disease than accidental TBI. Surprisingly, we found no significant differences in the associations between ICP and CPP and outcome in the AHT vs. accidental cohorts. This may in part reflect a somewhat smaller sample size of this population in our study (18 patients). However, in support of our findings, a recent paper analyzing a subset of our cohort of < 2y TBI subjects found a similar lack of association between ICP thresholds and outcome in infants with AHT and only a single CPP threshold, namely, CPP
