Inter- and Intra-Observer Variability in Transcranial Doppler (TCD) Technique in Neurocritical Care Patients
Conditions: Cerebral Aneurysm, Stroke, Vasospasm, Cerebral, Subarachnoid Hemorrhage, Aneurysmal, Aneurysmal Subarachnoid Hemorrhage, Cerebral Ischemia
Sponsor: Hackensack Meridian Health

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Inter- and Intra-Observer Variability in Transcranial Doppler (TCD) Technique in 
Neurocritical Care Patients 
Protocol No. 2019-0945 
NCT 04583163 
 
June 17, 2020 
 
 

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 Protocol No. 2019-0945 
 
Principal Investigator:  
Stephen M. Cohn, MD, FACS  
Sub-Investigator:  
Jyoti Sharma, MD, FACS, MPH 
Contact Information: 
Department of Trauma and Surgical Critical Care 
Hackensack University Medical Center 
30 Prospect Ave, Hackensack NJ 07601 
551-996-2609 
 
 
I.  
Summary 
 
This study aims to determine the inter- and intra-variability of Transcranial Doppler (TCD) ultrasound in 12 neuro- 
critical care patients who are planned for daily TCD evaluation. Up to 12 subjects will be recruited over a 1 year 
period.  Patients enrolled in the study are recruited from the pool of neuro-critical care patients admitted to the 
surgical intensive care unit (SICU) or surgical stepdown unit (3NTH).  The duration of the study will be 3 days per 
study subject. The study aims to determine the inter- and intra-variability of TCD ultrasound in neuro critical care 
patients who are planned for daily TCD evaluation. This study will also describe the change in velocity that prompts 
clinical intervention in symptomatic and asymptomatic vasospasm.  
II. 
Introduction and Background 
 
Vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a common serious complication estimated to 
affect 70-90% of patients, 30% of which are symptomatic.1,2  Vasospasm leads to poor outcomes (disability, death) 
and delayed cerebral ischemia (DCI).2  DCI is defined as focal neurological impairment, like hemiparesis, aphasia, 
hemianopia, or neglect or a global impairment, defined as a 2 point decrease on the Glascow Coma Scale (GCS).3  
DCI is a significant, often preventable outcome that can leave patients with permanent motor deficits, cognitive 
dysfunction, and reduced quality of life.3 Currently, vasospasm has been cited to be the sole causal mechanism of 
DCI.3  
The most common, least invasive modality to monitor vasospasm is transcranial Doppler (TCD) ultrasonography.2 
Multiple studies link increased TCD flow velocities to higher risk of DCI after aSAH, although the level and quality of 
evidence is weak.4,5 There is a paucity of data describing the accuracy and precision of TCDs as a tool for monitoring 
symptomatic vasospasm as predictor of DCI in aSAH. Most studies calculating the reproducibility and validity of TCDs 
are from more than 20 years ago and therefore may not reflect advances in technology and experience.6–8  
Furthermore, this published data primarily uses the Pearson correlation coefficient (r) to describe inter- and intra- 
observer agreement.  This statistic is inappropriate to measure the agreement between two variables which is better 
described using kappa or Bland-Altman analysis.9 
 
 
 

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This study aims to:  
1. Determine the inter- and intra-variability of TCD ultrasound in neuro critical care patients who are 
planned for daily TCD evaluation. 
2. Describe the change in velocity that prompts clinical intervention in symptomatic and asymptomatic 
vasospasm  
III. 
Inclusion Criteria 
 
1. Adults 18 years of age or older  
2. Current hospitalization for a neurologic issue and admitted to the surgical intensive care unit or surgical 
stepdown unit 
3. Undergoing daily transcranial Doppler imaging  
4. English or Spanish speaking patients and/or legally authorized representative (LAR)  
 
IV.  
Exclusion Criteria 
 
1. Less than 18 years of age 
2. Patient is unable to obtain consent and no LAR is  identified to provide consent 
3. Non-English or Non-Spanish speaking patients or LAR 
4. Unable to perform the study due to lack of availability of TCD technologists. 
 
V.  
Recruitment/Consent Procedures 
 
Up to 12 subjects will be recruited over a 1 year period.  Patients enrolled in the study are recruited from the pool 
of neurocritical care patients admitted to the surgical intensive care unit (SICU) or 3NTH.  No monetary incentive is 
offered. When the patients are admitted in the surgical ICU, the study staff will determine eligibility based on the 
protocol inclusion criteria. Due to the nature of the disease, there is a high likelihood that patients are either 
unconscious, of limited mental capacity and/or have been intubated therefore when appropriate the legally 
authorized representative will be utilized to obtain research consent.  
The research team will adhere to the guidelines pursuant to the HUMC policy 407-4: “Obtaining Informed Consent 
for a Research Study”, HUMC policy 1834: “Next of Kin”,  HUMC IRB Policy SOP IC 704 “Consent Requirements for 
Inclusion of Decisionally Impaired Subjects in Research” as well as New Jersey Statute 26:14-5 “Access to Medical 
Research Act”. No informed consent shall be obtained from a legally authorized representative if the participant is 
an otherwise competent person and will be able to provide adequate informed consent.  
 
 To meet study inclusion, transcranial Doppler (TCD) testing will be ordered as part of the standard of care for these 
patients. The test will not be ordered solely for research purposes. There are no known side effects from the non-
invasive measurement of cerebral blood flow using ultrasound. 
VI.  
Methodology 
Three different TCD technicians will do triplicate readings on 3 consecutive days on up to 12 patients already 
undergoing TCD as ordered by their treating team.   Standard of care on specific neuro critical care patients (such as 
cerebral aneurysms) is to undergo daily TCD monitoring to assess for possible vasospasm.   Patients will be in the 
supine position while measurements are obtained. The probe will be placed in the preauricular region of the 
temporal window. Patients will not be billed for the additional two TCD technicians obtaining readings.  
Day 1 (~ 15-30 minutes): TCD ultrasound will be performed at the bedside in the surgical ICU unit. The vascular 
technician will apply ultrasound gel to the transtemporal window. A bi-directional pulsed Doppler instrumentation 

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of 2MHz will be placed on the subject’s head at the trans-temporal window (Figure 1). Once the window is identified, 
the middle cerebral artery will be assessed at a depth of 40-60 mm with flow direction towards the transducer and 
an anterior spatial relationship. The estimated time to measure the cerebral blood flow of the MCA is 5-10 minutes.  
A mean and peak MCA flow velocity will be measured. Designated research coordinator will be present to document 
the measurements 
Day 2 (~ 15-30 minutes): TCD ultrasound will be performed at the bedside in the surgical ICU unit.  The vascular 
technician will apply ultrasound gel to the transtemporal window. The TCD probe will be gently applied to measure 
the cerebral blood flow (CBF) of the middle cerebral artery (mean and peak). The estimated time to measure the 
cerebral blood flow of the MCA is 5-10 minutes. Designated research coordinator will be present to document the 
measurements 
Day 3 (~ 15-30 minutes): TCD ultrasound will be performed at the bedside in the surgical ICU unit. The vascular 
technician will apply ultrasound gel to the transtemporal window. The TCD probe will be gently applied to measure 
the cerebral blood flow (CBF) of the middle cerebral artery. The estimated time to measure the cerebral blood flow 
of the MCA is 5-10 minutes. Designated research coordinator will be present to document the measurements 
 
 
Figure 1.  
It is anticipated that up to 20% of subjects may have an insufficient temporal bone window making TCD 
measurements difficult and/or inaccurate. This will be determined by the technician and these subjects will be 
considered as screen failures and excluded from further participation in the study.   
VIII. 
Study Endpoints 
 
Primary Endpoint: 
• 
The peak and mean flow velocity of the middle cerebral artery (MCA) 
• 
The peak and mean flow velocity of the posterior cerebral artery (PCA) 
• 
The peak and mean flow velocity of the basilar arteries 
 
IX. 
Statistical Analysis 
The continuous variables (such as: flow velocity) will be summarized using mean, median, standard deviation, 
interquartile range, range, minimum and maximum. The categorical variables (such as: gender of participant) will be 
summarized using frequency and percentage. To measure the intra-variability (within each TCD technician), the 
intraclass correlation coefficient will be calculated.10  To measure the inter-variability (between the TCD technicians), 
the Bland-Altman approach will be used.11  The 95% confidence interval on the variables of interest will be calculated. 
When necessary, graphical techniques will be used to display the statistical results. Statistical analysis will be 
performed using the R language (R Core Team [2018]. R: A language and environment for statistical computing. R 

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Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/.) or SAS software, Version 
9.4 for Windows (SAS Institute Inc., Cary NC, USA. URL http://www.SAS.com). 
 
X. 
Discomfort and Risks 
There are no associated risks with TCD.  The ultrasound measurements are completely noninvasive. The studies will 
be done expeditiously to avoid inconveniencing the subjects. 
There is small risk of breach of confidentiality, however; once the subject completes the three visits, the data 
collected will be fully de-identified.  Coded data will be kept indefinitely. The key linking the codes to the subjects’ 
identities will be destroyed approximately 5 years after completion of data analysis. 
XI. 
Benefits 
There are no direct immediate benefits to patients.  This study in the long-term may help elucidate the variability 
and accuracy of TCD ultrasound.  
XII.  
Confidentiality 
Data will be collected and coded on a paper form which will be stored and locked in a cabinet in the trauma office 
(St. John, G 834).  The coded data will then be entered in REDCap, an on-line data entry and managing system. 
REDCap stands for Research Electronic Data Capture. Only designated research staff will enter the data and have 
access to the data.  
There is small risk of breach of confidentiality, however; once the subject completes the three visits, the data 
collected will be fully de-identified.  Coded data will be kept indefinitely. The key linking the codes to the subjects’ 
identities will be destroyed approximately 5 years after completion of data analysis. 
Any publication or presentation resulting from this study will not identify any individual whose data was included 
in the analysis.  
 
 
 
 
 
 
 
 
 
 
 
 

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XII. 
Bibliography 
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Kumar G, Shahripour RB, Harrigan MR. Vasospasm on transcranial Doppler is predictive of delayed cerebral 
ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Neurosurg. 
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Francoeus CL, Mayer SA. Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit 
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Maeda H, Etani H, Handa N, et al. A validation study on the reproducibility of transcranial Doppler 
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9.  
Shen Q, Stuart J, Venkatesh B, Wallace J, Lipman J. Inter observer variability of the transcranial Doppler 
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