Một số yếu tố dự báo sớm KMT lan rộng và giá trị của thang điểm “spot sign” trong tiên lượng chảy máu não tự phát giai đoạn cấp tt tiếng anh

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY NGUYEN SONG HAO SOME EARLY PREDICTIONS OF HEMATOMA EXPANSION AND THE VALUE OF THE SPOT SIGN SCORE IN THE

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH

HANOI MEDICAL UNIVERSITY

NGUYEN SONG HAO

SOME EARLY PREDICTIONS OF HEMATOMA EXPANSION AND THE VALUE OF THE SPOT SIGN SCORE IN THE PROGNOSIS OF ACUTE SPONTANEOUS

INTRACEREBRAL HEMORRHAGE

Field of study : Intensive Care Medicine

Emergency and Clinical Toxicology Code : 62720122

SUMMARY OF MEDICAL DOCTORAL THESIS

HANOI – 2019

THE THESIS WAS COMPLETED AT:

HANOI MEDICAL UNIVERSITY

Scientific advisors:

1 Assoc.Prof Dr Nguyen Dat Anh

2 Assoc Prof Dr Vu Dang Luu

Reviewer 1: Assoc.Prof Dr Mai Xuan Hien

Reviewer 2: Assoc.Prof Dr Nguyen Van Chi

Reviewer 3: Assoc.Prof Dr Nguyen Van Lieu

The thesis defense shall be held by the university-level Thesis Assessment Board at Hanoi Medical University

Time: pm Date: , 2019

The thesis can be found at:

- Library of Hanoi Medical University

- National Library

LIST OF OF THE AUTHOR’S SCIENTIFIC ARTICLES

RELATED TO THE THESIS

1 Nguyen Song Hao, Nguyen Đat Anh, Vu Đang Luu (2019) A reserarch on some predicting factors of hematoma expansion after

primary intracerebral hemorrhage Vietnam medical journal, Vol

481 (1), 75-80

2 Nguyen Song Hao, Nguyen Đat Anh, Vu Đang Luu (2019) Predictive value of CTA spot sign and the role of spot sign score

on hematoma expansion and clinical outcome in intracranial

hemorrhage patients Vietnam medical journal, Vol 477 (1),

117-122

INTRODUCTION

1 The urgency of the study

Intracerebral hemorrhage (ICH)is a common neuropathy, with a high mortality rate, severe sequelae, a major burden for families and society Around the world, about 2 million people get ICH every year Although there are many modern facilities applied in diagnosis, treatment and resuscitation of stroke patients, the mortality rate in 30 days is still high, up to 30-50% About half of all deaths occur in the acute phase, especially in the first 48 hours

Hematoma expansion is a common and serious complication after ICH Although hematoma expansion is one of the major pathogenesis mechanisms in phases of ICH, it is also a serious complication after the acute phase The mechanism of hematoma expansion during the acute phase has not been clearly explained The spread of hematoma is an independent prognostic factor predicting the risk of death and adverse outcomes in patients with ICH

Many early predictions of hematoma expansion have been identified as: initial hematoma volume, irregular hematoma shape, consciousness disorder upon admission, time from onset to admission is short, using anticoagulants, heterogeneous hematoma density Some recent studies show that a new point of early predictions of hematoma expansion is the release of a contrast agent “extravasation contrast” or “spot sign” on computed tomography angiography cerebrovascular (CTA) in acute ICH The “spot sign” is the extravasation of the contrast agent located in the margin or center of the hematoma of the brain parenchyma, which can be seen with the naked eye on CTA films Delgado Almandoz (2010) have stated that “spot sign” and spot sign score values are independent prognostic factors, predicting the risk of death in inpatient treatment and poor outcomes at patients survived

In clinical practice, the scale helps clinicians evaluate patients quickly and effectively to promptly take the best measures to manage patients, making an important contribution to improving professional quality, increases healing ability

In the world there have been many researches on this issue In Vietnam, there are also some studies on some prognostic factors in ICH

by hypertension, but no research has fully evaluated the impact of risk factors predicting hematoma expansion as well as the value of the spot

sign score to predict the severity, risk of death and invalid in patients with ICH Detecting risk factors that predict hematoma expansion, and obtaining a truly valuable prognostic scale is an urgent requirement for clinicians, especially in emergency stroke management

From that fact, we carried out the research topic “Some early predictions of hematoma expansion and the value of the spot sign score

in the prognosis of acute spontaneous intracerebral hemorrhage”, aiming

at two goals:

1 Describe some of the early predictions of hematoma expansion

in patients with acute spontaneous intracerebral hemorrhage

2 Determine the value of the spot sign scorein the prognosis of acute spontaneous intracerebral hemorrhage patients

2 The layout of the thesis:

The thesis content consists of 137 pages with 40 tables (30 tables in the results section), 7 charts (5 of the results section) with the layout: Introduction (2 pages); Literature review (39 pages); Subjects and research methods (18 pages); Research results (30 pages); Discussion (45 pages); Conclusion (2 pages); Recommendation (1 page); References:

125 documents (Vietnamese and English)

3 New contributions of the thesis

This is the first study in the country to fully address the predictive factors of hematoma expansion in Vietnamese patients Research results

do not overlap with other studies in the country and abroad

The study identified the spot sign score value in prognosis of death, disability outcomes in inpatient treatment, and after 3 months of

treatment in patients with ICH

This research is a new contribution to clinical practice, helping clinicians, especially doctors in emergency departments, but not neurologists, to have a basis for assessing the prognosis Since then, there are

early management strategies and are suitable for patients with acute ICH

CHAPTER 1: LITERATURE REVIEW 1.1 OVERVIEW ABOUT HEMATOMA EXPANSION

1.1.1 Terminology and definitions

The term of hematoma expansion after spontaneous cerebral bleeding has never been used uniformly in scientific literature Therefore, many authors have defined hematoma expansion as all forms of spatial

expansion of initial bleeding including; Increased volume of hematoma

in the brain parenchyma, flowing into the ventricle or into the subarachnoid space adjacent to the original bleeding source and does not include formation of cerebral edema around the hematoma

The hematoma is determined to spread early when it occurs within the first 24 hours after the onset of spontaneous cerebal bleeding

1.1.2 Threshold determines hematoma expansion

The threshold for hematoma expansion has not been consistent across studies According to Steiner T (2010), the cut-off threshold is used to determine a significant spread of> 33% or> 12.5 ml According

to Wada R (2007), use the definition of> 30% or> 6ml and is supported

by previous studies of traumatic ICH showing the need for surgical intervention when the hematoma increases by 5ml According to Kazui (1996), hematoma was determined to spread by an increase of 12.5 ml or 1.4 times, which is the optimal cut-off threshold for assessing the spread

of the hematoma with the naked eye

1.1.3 Distinguish primary and secondary intracerebral hemorrhage

Non-traumatic cerebral bleeding is divided into 2 main subgroups of

primary ICH and secondary ICH:

Primary ICH accounts for about 78-88% of cases, resulting from rupture of small blood vessels whose background is not clear due to increased BP or powdered cerebrovascular disease The main risk factors for primary ICH are increased BP, powdered cerebrovascular disease, low blood cholesterol, alcohol, and tobacco

Secondary ICH occurs in lesser amounts, accounting for about 20%

of vascular abnormalities (cerebral vein malformations, aneurysms, cerebrovascular cavernome), newborn brain tumors, coagulopathy, trauma, drug abuse

1.2 SOME PREDICTABLE FACTORS OF HEMATOMA

EXPANSION

1.2.1 Short time from onset to hospitalization

A retrospective study of Fujii Y (1994) or Kazui (1996) demonstrated that patients who were hospitalized early, the time from onset of symptoms to short-first CT scans had a higher risk of hematoma

on CT scan next time

According to Fujii Y (1998), it has been shown that the short time from onset of stroke to CT scan is the most powerful prognostic factor for the spread of hematoma As previous studies have reported, the

prevalence of hematoma expansion decreases as the time from onset to hospitalization increases and spread of hematoma rarely occurs if the time from onset to when hospitalized> 6 hours

1.2.2 A disorder of consciousness when hospitalized

Fujii Y (1998) argues that the presence of consciousness disorder is

an independent predictable hematoma expansion, meaning that patients with consciousness disorders are likely to spread hematoma after hospitalize No previous studies have found an association between hematoma expansion and the degree of consciousness disorder Although

it is unclear about the high prevalence of hematoma for inpatient patients with conscious disorders The disorder of consciousness is representative

of a number of factors including hematoma size

1.2.3 Shape and density of hematoma

Bleeding that originates from a single point tends to appear enlarged lesions with uniform edges, developing from the center of the hematoma, the density of blood is more uniform When a bleeding originates from many points, there is almost an uneven edge lesions, and is developed from the junction of hematoma with brain organization The inhomogeneous density on cranial CT scans may reflect ongoing bleeding, more variable bleeding times and more points Heterogeneous blood flow is generated from many blood vessels, with low density spots, dilute blood just flowing beside high density blood clots

Barras C.D (2009), conducting research on the concept of abnormal hematoma shape and density on cerebral CT scans may predict the risk of hematoma expansion This concept comes from the view that uneven and heterogeneous hematoma may be the result of multiple bleeding points leading to an increased risk of hematoma expansion later

1.2.4 Low fibrinogen concentration

By Fujii Y (1998), multivariate analysis of hematoma expansion prediction factors, has published five independent prognostic factors related to hematoma expansion, in which low fibrinogen concentration is

an independent prognostic factor predicting hematoma expansion Therefore, decreased fibrinogen levels may be associated with the decline of both endogenous and exogenous coagulation mechanisms Therefore, low fibrinogen levels are considered as a risk factor as well as

a prediction of hematoma expansion

1.2.3 “spot sign” and prediction of hematoma expansion

The “spot sign” was first described in 1999 by Becker K.J The technique is carried out right after ICH diagnosis, detecting the escape of contrast into the hematoma The “spot sign” is correctly determined when there is an internal density of contrast dye in the brain parenchyma without an external blood vessel connection on vascular CT scans, described such as drops, zigzag points, or many points The “spot sign” has a maximum density that is usually twice the density of the hematoma, in a wide range of 100-200 Hounsfield units and size> 1.5mm Although basic histopathology of the “spot sign” is unknown The researchers suggested that the “spot sign” was formed from pathological changes related to extravasation from primary or secondary vascular injury

Definition of “spot sign”: There are many definitions in clinical practice

about “spot signs” However, according to Delgado Almandoz J.E (2010), the

“spot sign” is determined on CTA with the following four criteria:

- There is more than one point, the contrast stain is located in the brain parenchyma

- Density ≥ 120 HU

- Intermittent from normal blood vessels or damaged blood vessels adjacent to hematoma

- Any size and morphology

Distinguish “spot sign” and CTA techniques

The term “spot sign” changes in many studies and is often confused between a “spot sign” or “Contrast Extravasation” In order to elucidate the difference between the escape signal of the contrast agent into the hematoma on CTA scan and the CT scan after contrast injection through the studies, the term “spot sign” is now reserved for drainage of vascular contrast agent imaging into the hematoma on CTA capture, while the terminology of “Contrast Extravasation” is described as the presence of contrast agent on CT scans after injection

The “spot sign” on CTA is divided into two groups: the “spot sign”

in the early phase or the arterial phase (fisrt- pass CTA) is done within 30 seconds after contrast injection The “spot sign” in the late phase or intravenous phase (second-pass CTA) is performed within 40 seconds - 2

minutes after contrast injection

Distinguish images similar to “spot signs”: vascular and

non-vascular diseases such as arteriovenous malformations (AVM), dural

arteriovenous fistulas, ruptured aneurysms, giant thrombotic aneurysms, calcification in tumors, moyamoya disease is very Important because each pathology has different management strategies Other closely signs are calcification of the mesangial plexus and can be distinguished by CT

scans without contrast

1.2.4 Some other early predictable of hematoma expansion

Initial volume of hematoma: Dowlatshahi D (2011) retrospective

study on 496 patients; hematomas with volume less than 10ml are less likely to cause hematomas to spread and have better outcomes, whereas with hematoma > 30ml, it almost causes hematoma spread and ends bad Broderick J.P (1993) report that hematoma volume is best predicted for mortality in the first 30 days for all bleeding sites The initial hematoma and Glasgow volume had a strong and easy-to-use effect intended to report mortality and disability in ICH patients

Hypertension problem: Hypertension is a common problem in the

acute phase of ICH, accounting for over 70% of ICH patients Increased

BP may occur even in the absence of a previous history of hypertension and is an independent prognostic factor with poor outcomes Increasing

BP is a risk factor for hematoma expansion and increased mortality in ICH patients Prolonged systolic hypertension is associated with increased cerebral edema around hematomas Treatment to reduce BP may reduce the risk of hematoma expansion However, the evidence that

concluded this issue is not satisfactory

In addition, the problem of coagulation and the use of anticoagulants, alcohol abuse, internal factors were also mentioned by

some authors regarding the hematoma expansion after ICH

1.3 SPOT SIGN SCORE AND SOME PROGNOSTIC SCALES

1.3.1 Rationale for forming spot sign score

Delgado Almandoz (2009), research and development of the spot sign scoresystem, to find the most valuable characteristics to predict the spread of hematoma, as well as the prognosis of mortality and bad outcomes in ICH patients The structure of the spot sign scoreconsists of

3 components:

"Spot" number: 1 -2 spot: 1 point; ≥ 3 spots: 2 points

Maximum horizontal diameter: 1 - 4mm: 0 point; ≥ 5mm: 1 point

The largest density: 120 -179 HU: 0 point; ≥ 180 HU: 1 point

Table 1.1 Calculation of the Spot Sign Score

Spot Sign Characteristic points

1.3.2 Prognostic value of the spot sign score

Predictive hematoma expansion value of the spot sign score increases with the point of the scale, when the value of the scale is 0, the risk of hematoma expansion is 2% but the scale value is 4, the risk of hematoma expansion is 100%

Similarly, the spot sign score, which is an independent predictable risk of death in hospitals and has poor outcomes among survival patients when follow-up at the time 3 months

1.3.5 Some other prognostic score

1.3.5.1 Intracerebral hemorrhage score (ICH score)

The ICH score is based on 5 clinical indicators: age> 80, Glasgow scale, routine volume of CT hematoma at admission, hematoma location (upper or under tent) and the presence of signs of intraventricular bleeding The highest ICH score is 6 points, the lowest is 0 points However, with ICH under the tent, no patient achieved a score of 6 because there was no volume of hematoma> 30ml

1.3.5.2 FUNC score

The FUNC score was developed by Rost N.S in 2008, the structure consists of five components: initial hematopoietic volume, age, ICH position, glasgow point and cognitive deficiency before ICH The lowest score is 0 points, the highest is 11 points The FUNC score is the predictive outcome level in the acute phase, providing the most essential basic guidelines for clinicians and patients' families who are faced with decisions about treatment and care for patient and strategic options for clinical trials

1.3.5.3 Nine - Point Score

Brouwers H.B (2014), build a 9-point score based on data including: using warfarin when onset of symptoms, initial volume of hematoma,time from onset to initial CT scan, “spot sign” on CTA scan The highest score is 9 points, the lowest is 0 point From the data on the author successfully built a 9-point score to predict the hematoma expansion

CHAPTER 2: SUBJECTS AND METHOD

2.1 Participants

2.1.1 Inclusion criteria

- The time from onset to hospitalization ≤ 6 hours

- Age ≥ 18 years old

- Clinical: In accordance with AHA/ASA’s Stroke (2013): A stroke

is a sign that the brain’s dysfunction (localized or diffuse) progresses rapidly, lasting more than 24 hours or leads to death with no apparent cause other than of vascular origin Localized neurological symptoms are suitable for the brain area that damaged arteries are distributed, not due

- infratentorial intracerebral hemorrhage

- Secondary ICH (Cerebral aneurysm, cerebral vein malformations, trauma, drug abuse etc)

- Severe renal failure, CVA sequelae with mRS ≥ 3, end-stage cancer etc

- Death in 24 hours, or surgery before the second CT scan

- The patient or the patient's family does not agree to participate in the study

• d = 0.09 Is the desired accuracy

• Apply to the formula n = (1.96)2 x 0.32(1-0.32)/(0.09)2 = 103.2

• Minimum sample size in theory is 103 patients In this study, we selected 126 eligible patients

2.2.3 Method of sampling: convenience sampling

2.2.4 Location and time

The study was conducted at the Stroke Unit, ICU, Yen Bai Provincal General Hospital during the period from November 2014 to the

end of December 2018

2.2.5 Steps of the research

ICH patients meet the inclusion and exclusion criteria selected after approval for participation in the study

After asking diseases, examining and collecting data on age, gender, medical history (hypertension, alcohol abuse, use of anticoagulants, antiplatelet drugs, brain stroke, other pathologies), symptoms and onset time, clinical symptoms (Glasgow score, pulse, blood pressure, focal neurological signs) and ICH images on a CT scan of the skull at the first time when hospitalized (period from the onset to the time of capture, density, morphology and volume according to ABC/2 formula of hematoma), the patient is given blood tests (CBC, basic coagulation, hepatic and renal function) and computed tomography angiography cerebrovascular (CTA) to determine the “spot sign” according to the standard Delgado Almandoz, and to eliminate secondary ICH

All study patients were treated according to the general regimen: airway control, respiratory support, circulatory support, neurological

monitoring and evaluation, monitoring and examination at the Stroke Unit, Yen Bai Provincal General Hospital Steady patients have a CT scan of the brain for the second time after 24 hours, or whenever the patient shows signs of neurological impairment (Glasgow score decreases by ≥ 2 points, and / or signs of new paralysis or increased paralysis), the second CT scan was performed immediately Evaluation

of clinical symptoms (Glasgow score, pulse, blood pressure, focal neurological signs), time of imaging and image of ICH on the first brain CTA scan (density, morphology and volume by ABC / 2 formula of hematoma) The study patients were divided into two groups: Group I had hematoma expansion; Group II has non-hematoma expansion Hematoma expansion was assessed according to Wada (2007) and Park (2010) standards: ICH diagnostic criteria; volume of hematoma of cerebral parenchyma increased> 30% or> 6ml on the second CT scan compared with the first time (upon admission) Evaluate the shape and density of hematoma according to the standards of Barras C.D (2009) Comparing and analyzing the early predictive factors of hematoma expansion and determining the value of the spot sign scoreaccording to the research criteria

2.2.3 Data processing and data analysis: The research data was

collected according to the form of researched medical record, processed

and analyzed on medical statistics software

2.3 Ethical considerations

The patient or family member is explained about the purpose and method of the study Only patients or family members who represent legal patients who agree to voluntarily participate are included in the study Patients or family members representing legal patients have the right to discontinue participation in the study at any time