Transcranial Doppler as an Early Predictor of Neurological Outcome in Mild and Moderate Traumatic Brain Injury
Conditions: Trauma, Brain
Sponsor: Tanta University

Transcranial Doppler as an Early Predictor of
Neurological Outcome in Mild and Moderate
Traumatic Brain Injury
 
 
 
 
 
 استخدام الموجات فوق الصوتية عبر الجمجمة
 
 
 
 
 كمؤشر مبكر لتوقعات حالة الجهاز العصبي
 
 
 
 في إصابات المخ البسيطة والمتوسطة
Protocol Of Thesis
Submitted To
Faculty Of Medicine
Tanta University
 خطة بحث
 مقدمة إلى
 كلية الطب
 جامعة طنطا
In The Partial Fulfilment Of
Requirements Of M.D. Degree In
Anaesthesiology, Surgical Intensive
Care and Pain Medicine
 إيفاء جزئيا
 
 
 
 لشرط الحصول علي درجة
الدكتوراه
في
 
 
 التخدير والعناية المركزة الجراحية
 وعلج اللم 
Submitted by 
Mai Kamal Mohamed Abdallah
(M.sc.)
Tanta University
2020
 مقدمة من
 /الطبيبه
م 
 
 ي كمال محمددعبدالله
 
 
 ماجستير التخدير والعناية المركزة
الجراحية
 جامعة طنطا
2020
1

Introduction
 Traumatic brain injury (TBI) is a major cause of mortality and disability
worldwide. More than 80% of TBI cases presenting to the emergency room
(ER) are classified as mild to moderate (Glasgow Coma Scale (GCS) score,
9-15)1.
 Despite their apparent low severity on admission, mild and moderate
TBI can proceed to intracranial complications in up to 20% of cases, some of
which will require neurosurgical intervention 2,3. Crucially, patients with mild
to  moderate  TBI  are  also  susceptible  to  sudden  early  neurological
deterioration and described as the “patients who talk and die”4. 
Such  secondary  neurological  deterioration  (SND)  occurs  primarily
within the first week after injury and results from several causes: cerebral
edema,  intracerebral  or  subdural  hematoma,  subarachnoid  hemorrhage,
seizures, symptomatic hydrocephalus, or the cerebral consequences from
extracranial injuries5.
Detecting patients at risk for early SND after mild to moderate TBI on
admission has received relatively little attention. Most studies have been
conducted to identify predictors of unfavorable outcome at least 6 months
after mild or moderate TBI6, 7.
Biochemical serum markers such as protein S-100b have been used to
assess functional outcome, symptoms, and measures of neuropsychological
impairment several months after injury, not to screen patients at risk of early
neurological  complications8.  As  a  result,  most  emergency  management
protocols focus exclusively on using CT scans to identify the relatively small
number of patients who may require early neurosurgical procedures9, 10.
2

Transcranial Doppler (TCD) is a technique that explores cerebral blood
flow velocities11. In patients with TBI, this technique can reveal low diastolic
blood flow velocity (FVd) and high pulsatility index (PI) values induced by
high vascular bed resistance. TCD has been used on admission to improve
cerebral hemodynamics in patients with severe TBI12. Surprisingly, little
studies conducted in patients with mild and moderate TBI. 
In a study by Bouzat et al., 2011, including patients with normal or mild
brain lesions on initial CT scan, they found a correlation between TCD
measurements on admission and early neurologic status. The thresholds of
1.25 and 25 cm/s for PI and FVd accurately predicted neurologic worsening
with 90% sensitivity and 91% specificity2.
Also, cohort study by Bouzat et al., 2016, found that TCD measurement
threshold had high negative predictive value (NPV) to predict neurological
worsening despite low incidence while the positive predictive value (PPV) of
TCD to predict SND was low5.
As it was a limitation in previous study, we will use wider range of
threshold rather than strict cutoff threshold. 
3

Aim of the work
The aim of our research will be to study the utility of Transcranial
Doppler Pulsatility Index in mild and moderate traumatic brain injury for
early prediction of neurological deterioration.
4

Patients and methods
This  prospective  study  will  be  carried  out  in  Tanta  Emergency
Hospitals for one year starting after approval from Ethics Committee on 105
patients with mild to moderate traumatic brain injury (TBI). 
After  approval  from  Institutional  Ethics  Committee  an  informed
consent will be obtained from each participant. All data of patients will be
confidential with secret codes and private file for each patient. All given data
will be used for the current medical research only. 
Any unexpected risks appeared during the course of the research will
be cleared to participants and the ethical committee on time. Each participant
will receive an explanation to the purpose of the study and have secret code
number to ensure privacy to participants and confidentiality of data.
Inclusion criteria:
 Any adult patient aged (25_60) years presented with mild to moderate
TBI  (GCS  9  –  15)  admitted  to  Emergency  Hospitals  within  12  hours
following the trauma.
Exclusion criteria:

 Patient underwent head surgical procedure before admission.

 History of previous intracranial lesion.

 History of treatment with anticoagulant and /or antiplatelet.

 TBI more than 12 hours following trauma.

 Mechanically ventilated patients with sedation on admission.

 Systolic arterial blood pressure less than 90 mmHg and /or arterial
pulse oximetry less than 90%.
5


 Evidence of severe brain lesions on initial CT scan (i.e., Traumatic Coma
Data Bank TCDB classification III-VI)14

 Any craniotemporal lesion impeding satisfactory TCD examination
Each patient will be undergoing:

History (from patient and attendance).

General and neurological examination.

Monitoring (noninvasive blood pressure, Electrocardiography, oxygen
saturation (SaO2))

Laboratory investigation( Hb concentration, serum Na and K 
concentration and arterial blood gases (ABG))

Equipment:
Doppler Ultrasound machine (SonoScape®, SSI-6000, China). 
Ultrasound probe 2 - 5 MHz.
Sterile gloves, towels and gel.

Method:
Both  middle  cerebral  arteries  will  be  insonated  through  the
transtemporal window at a depth of 50 to 60 mm, and tracings will be
recorded for at least 10 cardiac cycles in patients showing stable conditions,
i.e., no agitation or pain, no cardiorespiratory distress. The clinoid process
of the sphenoid bone and the brain stem will be initially identified. Color-
coded sonography will enable identification of the circle of Willis. The
middle  cerebral  artery  (MCA)  will  be  identified  and  manual  angle
correction then will be applied to measure blood flow velocity in each MCA
(in centimeter per second). Tracings will be stable over a 30-s recording
period. Time-averaged mean blood flow velocity (FVm), systolic blood
6

flow velocity (FVs), diastolic blood flow velocity (FVd) (in centimeter per
second) and the PI [(FVs – FVd)/FVm] will be calculated2.
All patients will have TCD measurements immediately on admission
and will be classified into groups according to PI value and the outcome.
Measurements
 
 :   
 All data will be recorded by a physician not included in the research.

Age,  sex,  Glasgow  coma  scale13,  comorbidities  and  the  cause  of
trauma.

The length of stay in the hospital and ICU.

The heart rate, blood pressure, Sao2 and Paco2 every 12 hr in first 48 hr 
then every day till 7th day. 

Head CT classification by (TCDB classification) 14 on admission.

Pulsatility index (PI) will be measured on admission then every 12hr
following admission for 1st 48 hour after that every day till 7th day.

Secondary neurological deterioration (SND)15 (one of the two objective
criteria: (1) a decrease in GCS of greater than 2 points from the initial
GCS in the absence of pharmacologic sedation (2) a deterioration in
neurologic status sufficient to warrant intervention,  i.e., mechanical
ventilation, sedation, osmotherapy, or neurosurgical intervention) after
48hr till the 7th day.

Extended Glasgow Outcome Scale (GOSE) 13after one month.
Primary outcome:
SND at 7th day post traumatic.
Secondary outcomes:
Length of stay in ICU and GOSE after one month.
7

Sample Size Calculation:
Using MedCalc program version 18.2.1 (MedCalc Software, Ostend,
Belgium), the sample size is calculated as 105 patients. The sample size
calculated by the following criteria:

5% confidence limit. 

80% power of the study.

According to a previous study (2), area under the curve (AUC) for PI 
to predict the outcome (SND) was 0.86 and 6% of patients developed
SND within the first week after trauma.

16 cases were added to overcome drop out.
8

Results
All results will be tabulated and statistically analyzed.
9

Discussion
The results will be discussed later.
10

References
1) Thornhill S, Teasdale GM, Murray GD, et al.  Disability in young
people and adults one year after head injury: prospective cohort study.
Bmj. 2000 Jun 17;320(7250):1631-5
2)  Bouzat P, Francony G, Declety P, et al. Transcranial Doppler to screen
on  admission  patients  with  mild  to  moderate  traumatic  brain  injury.
Neurosurgery. 2011 Jun 1;68(6):1603-10.
3) Compagnone C, d'Avella D, Servadei F, et al. Patients with moderate
head injury: a prospective multicenter study of 315 patients. Neurosurgery.
2009 Apr 1;64(4):690-7.
4) Davis DP, Kene M, Vilke GM, et al. Head-injured patients who “talk and
die”:  the  San  Diego  perspective.  Journal  of  Trauma  and  Acute  Care
Surgery. 2007 Feb 1;62(2):277-81.
5) Bouzat P, Almeras L, Manhes P, et al. Transcranial Doppler to predict
neurologic  outcome  after  mild  to  moderate  traumatic  brain  injury.
Anesthesiology: The Journal of the American Society of Anesthesiologists.
2016 Aug 1;125(2):346-54.
6) Fabbri  A,  Servadei  F,  Marchesini  G,  et  al.  Early  predictors  of
unfavourable  outcome  in  subjects  with  moderate  head  injury  in  the
emergency department. Journal of Neurology, Neurosurgery & Psychiatry.
2008 May 1;79(5):567-73.
7) Wardlaw JM, Easton VJ, Statham P. Which CT features help predict
outcome after head injury?. J Neurol Neurosurg Psychiatry. 2002 Feb
1;72(2):188-92..
8) Townend W, Ingebrigtsen T. Head injury outcome prediction: a role for
protein S-100B?. Injury. 2006 Dec 1;37(12):1098-108.
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9) af  Geijerstam  JL,  Oredsson  S,  Britton  M. Medical  outcome  after
immediate computed tomography or admission for observation in patients
with  mild  head  injury:  randomised  controlled  trial.  Bmj.  2006  Aug
31;333(7566):465.
10)  Stein SC, Burnett MG, Glick HA. Indications for CT scanning in mild
traumatic brain injury: a cost-effectiveness study. Journal of Trauma and
Acute Care Surgery. 2006 Sep 1;61(3):558-66.
11) Bouzat P, Oddo M, Payen JF. Transcranial Doppler after traumatic
brain injury: is there a role?. Current opinion in critical care. 2014 Apr
1;20(2):153-60.
12) Ract C, Le Moigno S, Bruder N, et al. Transcranial Doppler ultrasound
goal-directed therapy for the early management of severe traumatic brain
injury. Intensive care medicine. 2007 Apr 1;33(4):645-51.
13)  Wilson JL, Pettigrew LE, Teasdale GM. Structured interviews for the
Glasgow  Outcome  Scale  and  the  extended  Glasgow  Outcome  Scale:
guidelines for their use. Journal of neurotrauma. 1998 Aug;15(8):573-85.
14) Marshall LF, Marshall SB, Klauber MR, et al. A new classification of
head injury based on computerized tomography. Journal of neurosurgery.
1991 Nov 1;75(Supplement):S14-20.
15) Morris GF, Juul N, Marshall SB, et al. Neurological Deterioration as a
Potential Alternative End point in Human Clinical Trials of Experimental
Pharmacological Agents for Treatment of Severe Traumatic Brain Injuries.
Neurosurgery. 1998 Dec 1;43(6):1369-72.
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