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Current Opinion and Use of TCD in Pediatric Severe TBI Kerri L. LaRovere MD Assistant in Neurology Boston Children’s Hospital
Current Opinion and Use of TCD in Pediatric Severe TBI
Kerri L. LaRovere MDAssistant in Neurology
Boston Children’s Hospital
DISCLOSURES
Kerri L LaRovere has no conflicts of interest or financial disclosures to make
The content of this presentation does not contain reference to, nor advocates use of, unlicensed medicines or devices
Objectives
▪ Review epidemiology of pediatric severe traumatic brain injury (TBI)
▪ Discuss clinical and research applications of TCD in severe pediatric TBI
3
Prevalence of Acute Neurological Disease in Children: A Global Epidemiological Assessment (PANGEA) Study, PI: Fink
Objective: Measure global burden of pediatric
neurological injury and describe variations in
interventions and outcomes in intensive care
units
Study design: International, prospective, point
prevalence study on 4 study dates during
2011 – 2012
Inclusion criteria: Children aged 7 d – 17 years
admitted to an ICU with cardiac arrest , TBI,
status epilepticus, CNS infection, stroke, brain
mass, spinal cord injury, hydrocephalus
Exclusion criteria: Perinatal or remote CNS
insult
Study sites: 107 ICUs, 23 countries, 6 continents
Fink E. et al. 2017, p.330-342.
PANGEAPrevalence of Acute critical Neurological disease in children:
a Global Epidemiological Assessment
5
20% with TBI
9% mortality
50% with unfavorable cognitive outcomes at 3 months
(N=831)
Fink E. et al. 2017, p.330-342.
Economic costs of severe TBI in PANGEA (2009 USD)
▪ Length of hospital stay was main driver of cost
▪ 4th highest length of stay
▪ 4th highest hospital cost
6Unpublished data. Courtesy of Ericka Fink, MD.
Objectives
▪ Review epidemiology of pediatric severe traumatic brain injury (TBI)
▪ Discuss clinical and research applications of TCD in severe pediatric TBI
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Survey of TCD in Pediatric Critical Care (N=29 centers)
Unpublished data
Questions
• Is there "raised ICP“?
• Is autoregulation intact or not?
• Is traumatic vasospasm present?
• Is there unappreciated vascular injury?
• Is this patient in a poor prognostic category?
Udomphorn et al. 2008, p225-234.
Normal CBF/CBFV in adults
CBFV is higher in children compared to adults
Age MCA ICA ACA PCA BA
Systolic peak velocity:
0-10 days
11-90 days
3-11.9 months
1-2.9 years
3-5.9 years
6-9.9 years
10-18 years
Mean flow velocity *:
0-10 days
11-90 days
3-11.9 months
1-2.9 years
3-5.9 years
6-9.9 years
10-18 years
End diastolic peak velocity:
0-10 days
11-90 days
3-11.9 months
1-2.9 years
3-5.9 years
6-9.9 years
10-18 years
46 (10)
75 (15)
114 (20)
124 (10)
147 (17)
143 (13)
129 (17)
24 (7)
42 (10)
74 (14)
85 (10)
94 (10)
97 (9)
81 (11)
12 (7)
24 (8)
46 (9)
65 (11)
65 (9)
72 (9)
60 (8)
47 (9)
77 (19)
104 (12)
118 (24)
144 (19)
140 (14)
125 (18)
25 (6)
43 (12)
67 (10)
81 (8)
93 (9)
93 (9)
79 (12)
12 (6)
24 (8)
40 (8)
58 (5)
66 (8)
68 (10)
59 (9)
35 (8)
58 (15)
77 (15)
81 (19)
104 (22)
100 (20)
92 (19)
19 (6)
33 (11)
50 (11)
55 (13)
71 (15)
65 (13)
56 (14)
10 (6)
19 (9)
33 (7)
40 (11)
48 (9)
51 (10)
46 (11)
-
-
-
69 (9)
81 (16)
75 (10)
66 (10)
-
-
-
50 (12)
48 (11)
51 (9)
45 (9)
-
-
-
35 (7)
35 (9)
38 (7)
33 (7)
-
-
-
71 (6)
88 (9)
85 (17)
68 (11)
-
-
-
51 (6)
58 (6)
58 (9)
46 (8)
-
-
-
35 (6)
41 (5)
44 (8)
36 (7)
Bode H, Wais U. 1988, p606-11.
CBFV in Healthy Children
N=112 subjects
CBFV in the PICU(N=140 patients)
Across ages,
MCA MFV are significantly lower than age matched, healthy children
Should this data be used as reference for PICU patients?
PSV
EDV
MFV
O'Brien NF. 2015, p2269-76 (Reproduced with permission from author).
LaRovere KL, O’Brien NF, Tasker RC. 2016, p2105-2114.
Search terms:“ultrasonography Doppler transcranial” OR “TCD,” OR “transcranial Doppler,” “autoregulation,” OR “cerebrovascular
Inclusion:≥5 cases were in a case series, subjects <18 yrs, and TCD performed in the PICU
Reference. Author (Year)
DesignCountry (n)
Period Disease Device Period (Months)
Indication
Vavilala et al. (2006)
ProspectiveUSA (28)
May 2003 – March 2005
TBI, GCS<9 Multidop X 36 Autoregulation
Vavilala et al. (2007)
ProspectiveUSA (10)
May 2003 –February 2006
TBI, GCS<9 Multidop X 36 Autoregulation
Tontisirin et al. (2007)
ProspectiveUSA (9)
June 2004 –August 2006
TBI, GCS<8 Multidop X 27 Autoregulation
Vavilala et al. (2008)
ProspectiveUSA (42)
June 2004 –August 2006
TBI, GCS≤12 Multidop X 27 Autoregulation
Freeman et al. (2008)
ProspectiveUSA (37)
May 2002 – June 2007
TBI, GCS<13 Multidop X 60 Autoregulation
Chaiwat et al. (2009)
ProspectiveUSA (36)
May 2002 –October 2007
TBI, GCS<9 Multidop X 60 Autoregulation
Philip et al. (2009) ProspectiveUSA (42)
NR TBI, GCS<9 Multidop X NR Autoregulation
Visocchi et al. (2007)
ProspectiveItaly (6)
NR TBI, GCS<8 NIC Vue NR Intracranial hypertension
Figaji et al. (2009a) ProspectiveSA (34)
June 2006 – May 2008
TBI, GCS≤8 Smart-lite 24 Intracranial hypertension
Figaji et al. (2009b)
ProspectiveSA (24)
June 2006 – May 2008
TBI, GCS≤8 Smart-lite 24 Autoregulation
Figaji et al. (2010) ProspectiveSA (28)
NR TBI, GCS≤8 Smart-lite NR Response to normobaric hyperoxia
O’Brien et al. (2010)
ProspectiveUSA (22)
May 2007 – March 2009
TBI, GCS≤12 Companion III 10 Vasospasm
O’Brien et al. (2014)
ProspectiveUSA (69)
NR TBI, GCS≤12 Sonara NR Vasospasm
Obrien et al. (2015) ProspectiveUSA (36)
NR TBI, GCS≤8 Sonara NR Intracranial hypertension
Scavarda et al. (2010)
ProspectiveFrance (36)
1991 – 2000 TBI, GCS 3 – 15 NR 120 Prognosis
Moftakhar et al. (2015)
RetrospectiveUSA (37)
1990 – 2013 Aneursym and TBI, GCS≤12
Neuroguard 276 Vasospasm
TCD in Severe Pediatric TBI (Dec 2015 – 2018)
Search Strategy PubMed
2015 - 2018
Search terms (All fields and MeSH terms):“ultrasonography Doppler transcranial” OR “TCD” OR “transcranial Doppler”
2,015 citations
774Adult TCD
studies
113Pediatric TCD
studies
16 Studies in
PICU
≥5 cases for case series,subjects <18 yrs, and TCD performed in the PICU
4Studies in
TBI
1,128Other
1 VSP, 1 CA (CO2
reactivity), 2 CBFV and outcome
Is There “Raised” Intracranial Pressure?
ICP 45 mmHg ICP 50 mmHg ICP > 60 mmHg
Reproducible, progressive waveform changes as ICP rises
ICP is Age-Related
Newborn 0.7 – 1.5 mmHg
Infant 1.5 – 6.0
Children 3.0 – 7.5
Adult <10 – 20
Pediatric severe TBI guidelines:
>20 mmHg may be considered pathologic
Kochanek et al. 2012, p.S1 - S82.
Intracranial Hypertension
Study N Variable Results
Figaji et al. 2009 34 PI ICP≥20 mmHg could be detected with 25% sensitivity and 80% NPV if PI 1.0 was used. Using PI 1.2 did not improve sensitivity. Pre-test/post-test probability: 22%, 38%.
Obrien et al. 2015
36 PI Using PI>1.31 within 24 hours of admission, ICP≥20 mmHg could be predicted with 100% sensitivity and 82% specificity (n=8). Pre-test/post-test probability: 22%, 62%.
CBF=CPP/k
Static rate of autoregulation (SROR)
• SROR = %ΔeCVR/%ΔCPP (or ABP)
• eCVR = CPP (or ABP)/CBFV
• Results range 0 (absent) to 1.0 (intact autoregulation)
CPP
2 – 6 years 50 mmHg
7 – 10 years 55
> 11 years 60
Pediatric severe TBI guidelines:
“A minimum CPP of 40 mm Hgmay be considered in children with TBI…”
Kochanek et al. 2012, p.S1 - S82.
Is autoregulation intact or not?
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Study Period Age (years)
TBISeverity
Induction Stimulus Timing Frequencyof Exams
Incidence ARI<0.4
Vavilala et al. 2006
May 2003 –March 2005
1.3 – 17 GCS<9 Phenylephrine CPP PID 0 – 3 1 43%
Vavilala et al. 2007
May 2003 –February 2006
0.8 – 5 GCS<9 Phenylephrine CPP PID 0 – 2 1 80%
Tontisirin et al. 2007
June 2004 –August 2006
5 – 15 GCS<8 Phenylephrine CPP PID 0 – 10 ≥ 2 33%
Vavilala et al. 2008
June 2004 –August 2006
5 – 15 GCS<13 Phenylephrine CPP PID 0 – 9 1 36%
Freeman et al. 2008
May 2002 –June 2007
0.8 – 16 GCS<13 Phenylephrine CPP PID 0 – 3 1 27%
Chaiwat et al. 2009
May 2002 –October 2007
0.8 – 16 GCS<9 Phenylephrine CPP or mBP
PID 0 – 3 1 39%
Philip et al. 2009
NR 0.8 – 16 GCS<9 NR mBP PID 0 – 3 1 25%
Figaji et al. 2009
June 2006 –May 2008
1 – 11 GCS<9 Phenylephrine mBP NR >1 29%
Incidence of impaired autoregulation (SROR) varied from 25% to 80%
Monitoring autoregulation continuously as a correlation coefficient to CPP (e.g. TCD-based Mx index) may be an alternative approach.
Study Period Disease Variable ResultVavilala et al. 2006
May 2003 – March 2005
Severe TBI
ARI No association between ARI and GOS at hospital discharge or 3 months. At 6 months, 67% (8/12 patients) with ARI<0.4 had unfavorable outcome versus 88% with intact ARI had favorable outcome (p=0.005). ARI<0.4 predicted 6 month GOS<4 with 80% sensitivity, 78% specificity positive predictive value 67%, and negative predictive value 88%.
Tontisirin et al. 2007
June 2004 – August 2006
Severe TBI
ARI 2/3 patients with impaired autoregulation had unfavorable outcome at 12 months and 1/3 patients with absent autoregulation had favorable outcome.
Freeman et al. 2008
May 2002 – June 2007
Severe TBI
ARI GOS<4 was associated with lower ARI values and impaired autoregulation at 12 months.
Chaiwat et al. 2009
May 2002 – October 2007
Severe TBI
ARI, Vmca<2SD ARI<0.4 was independent risk factor for unfavorable outcome at 6 months by multivariate analysis (adjusted OR 29.8; 95% CI 1.7-521.4). Vmca<2SD occurred in 17% (6/36 patients) and was significantly associated with unfavorable 6 month GOS on univariate analysis (p=0.04) but not by multivariate logistic regression.
Figaji et al. 2009
June 2006 – May 2008
Severe TBI
ARI No association with ARI and 6 month GOS.
No consistent relationship between SROR and outcomes
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Is traumatic vasospasm present?
Patient Summary: 15 year old boy with a gun shot wound
Mild Vasospasm, Day 6 Moderate Vasospasm, Day 7
TCD Impression: MCA MFV >2SD (103 cm/s) above normal for age and LR>3. Findings correlated with evidence of vasospasm on MRA, CTA, DSA.
Is traumatic vasospasm present?
Traumatic Vasospasm
Study Disease (n) Criteria Incidence Timeline
O’Brien et al. 2010
TBI, GCS≤12 (22)
Adult(MFV>120cm.s-1 and LR ≥3)
MCA: 36% Onset: 2-3 daysDuration (MCA): 3 ± 1 days
O’Brienet al. 2014
TBI, GCS≤12 (69)
Pediatric(CBFV>2SD above normal for age and LR ≥3)
MCA: 28% Onset (MCA): 4 ± 2 daysDuration (MCA): 2 ± 2 days
Moftakhar et al. 2015
aSAH, tSAH, GCS≤12
(37)
Adult DSA: 46% (n=17); TCD: 81% (n=16)
Pre-test/post-test probability: 32%, 45%
Onset (DSA): 7 ± 5 daysOnset (TCD): 5 ± 3 daysDuration: 7.5 ± 3 days
Adult TCD criteria for vasospasm overestimate the prevalence of vasospasm in children
Is there unappreciated vascular injury?
• Blunt cerebrovascular injury occurs in children
• Bonnow et al. 2018:
– 1.3% (96/7,440) of pediatric trauma admissions
– 18% (17/96 admissions) stroke rate
• In adults, emboli detection by TCD is associated with increased risk of BCVI-related stroke
• Further research using emboli detection in children may identify those with underappreciated BCVI
25Bonnow et al. 2017, pe1011-e1017; Bonnow et al. 2018, p.50-57.
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Study Design TBI Method N Age
Post-
Injury
Day ResultsMaugans et al. 2012 Prospective Mild/
Concussion
MR
angiography
12 11-17 years 0-3, 14,
30
Early low CBF, remained low in
1/3 >30 days
Adelson et al. 2011 Retrospective Severe Stable Xenon
CT
95 0-18 years 0-9 Early low CBF associated with
worse outcomes
Watermark et al. 2005 Prospective Moderate CT perfusion 14 7 days – 18 years 0 Lower regional CBF and CBV in
contusions
Adelson et al. 1997 Retrospective Severe Stable Xenon
CT
30 ≤8 yrs 0-9 Early low CBF assoc with worse
outcomes
Sharples et al.1995 Prospective Severe Kety-Schmidt
(N2O)
21 2-16 years 5.75-50
hours
Low CBF related to ICP
elevations, hyperemia rare
Muizelaar et al 1989 (Part 1) Retrospective Severe 133Xe 32 3-18 years 0-3 Early low CBF with later relative
hyperemia
Muizelaar et al 1989 (Part II) Retrospective Severe 133Xe 26 13±4.7 years Not
stated
CBF not associated with any
variable, including outcome
Bruce et al 1981 Retrospective Severe 133Xe 6 16-21 years Not
stated
Elevated CBF related to
hyperemia and diffuse swelling
Kassoff et al 1972 Retrospective Severe 133Xe 10 9 months-12 years 2.5 hours
to 2
months
Regional increase in CBF in 6/10
patients
Early reduction in global CBF < 20 ml/100gm/min is associated with unfavorable outcome
Study Period Disease Variable Result
Visocchi et al. 2007
NR Severe TBI Vmca Vmca>2SD occurred at some point in 67% (4/6). GOS<4 in all patients at 1.2 – 9 years follow up.
Chaiwat et al. 2009
May 2002 –Oct 2007
Severe TBI ARI, Vmca ARI<0.4 was independent risk factor for unfavorable outcome at 6 months by multivariate analysis (adjusted OR 29.8; 95% CI 1.7-521.4). Vmca<2SD occurred in 17% (6/36 patients) and was significantly associated with unfavorable 6 month GOS on univariate analysis (p=0.04) but not by multivariate logistic regression.
O’Brien et al. 2018
NR Moderate to Severe TBI
(n=34)
Vmca <2SD in 4/69 (4%), ±2SD in 30/49 (43%), >2SD with LR<3 in 16/69 (23%), >2SD with LR≥3 in 19/69 (28%). None with low flow had GOS-EPeds ≤4 (favorable).No association with differences in neuropsych measures at 12 mo (n=49).
Alterations in CBFV and Outcomes
• CBFV alterations are heterogeneous during first week following TBI
• CBFV <2SD for age may be associated with unfavorable neurologic outcomes
• Favorable outcomes may be more likely with normal CBFVs
Limitations
• Lack of population parameters
• Lack of validated criteria
• Sample size
• Clinical heterogeneity (e.g. mixed “phenotypes,” variation in local TBI practices?)
• Variation in research methodology (e.g. measurements, outcomes, data interpretation)
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Summary
• Severe pediatric TBI is a global health problem
• TCD may be a useful tool to assess autoregulation, intracranial pressure, and vasospasm in the PICU for TBI
• Further research is needed to validate findings and establish gold standards in children
• Then TCD may impact day-to-day management in the PICU and improve outcomes in children with severe TBI
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