Download 評估嚴重頭部外傷處理準則對病患存活情形及健康相關生活品質之衝擊

Title of Application：Assessment of Guidelines of Management in Severe Head
Injury
評估嚴重頭部外傷處理準則對病患存活情形及健康相關生活品質之衝擊
頭部外傷照護之主要目的是降低其死亡率及殘障程度，並盡可能的提高傷者之生活
品質。自 1970 年以來，許多報告指出對於嚴重之頭部外傷病患採用加護重症照顧可顯著
降低死亡率及殘障程度，美國更於 1995 年正式發表嚴重頭部外傷處理準則（Guidelines of
management in severe head injury），其中主張嚴重病患應裝置顱內壓（Intracranial pressure,
ICP）監測，除了強調顱內壓的控制外，更應著重於腦灌流壓（Cerebral perfusion pressure,
CPP）的維持，藉此以避免腦部缺血所造的細胞壞死，這種新觀念與傳統的治療方法截然
不同，甚至背道而馳。此突破性知識已在歐美國家廣泛實施，而且經過五年之評估，認為
此一新觀念確實有其臨床效果。
然而，目前台灣對此新觀念尚未完全接受，有些神經外科醫師甚至採存疑的態度，
因此在提倡依照準則的新觀念時，常由於本土性的相關研究佐證不夠而有爭議，甚至受到
阻礙。有鑑於此，建立依全台灣人口為基礎之研究，提供有力之證據，實為刻不容緩之工
作，藉此以加速推動醫療機構接受此新觀念，進而造福病人。
本研究之目的在於藉由持續性的登錄全國頭部外傷資料，瞭解目前台灣之醫療機構，
使用 ICP 監測之新照護準則的情況，並利用 Glasgow Outcome Scale(GOS)及 CPP 療程存活
追蹤 Health-related Quality of Life(HRQL)調查以瞭解是否應用 ICP 監測及 CPP 照護之嚴重
頭部外傷病患其預後及健康相關生活品質之差異情形。另外並將針對神經外科醫師，舉辦
數場演講及研討會以宣導新的照護觀念，並於一年後重新評估其效益。
研究之進行方式可略分為以下之六步驟：
一、全國頭部外傷資料登錄，並由登錄資料中找出嚴重之頭部外傷患者。
二、重新審閱嚴重頭部外傷病患之病歷，並將之區分為如下述之三個族群以比較預後之差
異。
1.有顱內壓監測及腦灌流壓照護管理之病患；
2.有顱內壓監測，但無腦灌流壓照護管理之病患；
3.無顱內壓監測，亦無腦灌流壓照護之頭部外傷病患。
三、以 HRQL 問卷持續追蹤此三目標族群之存活結果及健康相關生活品質，以進行評估及
比較此三組間差異。
四、訪視神經外科醫師其 CPP 照護之經驗，故可藉此而評估國內神經外科醫師對此新照
護準則之瞭解程度及實際實施情形。
五、於計畫中期舉辦各講座、講習以有效協助神經外科醫師對於「嚴重頭部外傷處理準則」
之認知與瞭解。
六、藉由瞭解國內醫療機構使用顱內監測及腦灌流壓照護比率之變化，以評估「嚴重頭部
外傷處理準則」宣導之成效。
Abstract
The objective of head injury management is primarily to reduce the mortality rate and
disability, and to promote the quality of life (QOL) from the unfortunate. A large body of
published data reports that significant reductions in mortality and morbidity can be achieved in
patients with severe head injury by using intensive management protocols. Of the recent
“Guideline of Management in Sever Head Injury” developed by the American Association of
Neurological Surgeon and the Brain Trauma Foundation since 1995, intensive monitoring of
intracranial pressure (ICP) is essential in determining the adequate cerebral perfusion pressure
(CPP) and thus, salvage the swelling brain from further ischemia. This break through
knowledge has been greatly implicated as the guideline in U.S. and Euro-countries. New
protocols provide converse view from the earlier management of decompression. New idea
suggested that poor cerebral perfusion could be harmful, and a somewhat elevated blood
pressure could protect against brain ischemia in a patient with high ICP. After the assessment
for 5 years, magnificent results have been observed in clinical trials. However, Taiwan is still
absent in providing evidence-based research and promotion of the significance of ICP
monitoring while lack of study in Taiwan has also resulted in great controversy over the issue of
adequate CPP management. Thus, a population base study in Taiwan is not only mandatory in
resolving the debate of the issue and further, in pushing the application of new protocols in
major health institution.
From the continuation of prior data registry, the purposes of our research are to understand
the current status in the implication of “Guideline of Management in Severe Head Injury”
involving the use of ICP monitoring among major heath institutions in Taiwan, to investigate the
outcome difference (Glasgow Outcome Scale (GOS) & Health-related Quality Of Life (HRQL) )
among patients with severe head injury (Glasgow Comma Scale (GCS)≦ 8) after the
application of ICP monitoring and CPP based management in Taiwan, and to re-evaluate the
effectiveness after one year of promotion by providing lectures and symposium for
neurosurgeons regarding the use of “Guideline of Management in Severe Head Injury”.
Method of the study will be addressed in six major approaches:
1.Head injury data registration to find out severe head injury population.
2.Review the medical chart of patients with severe head injury. According to the review,
patients will further be divided into three groups as followed and will be assessed and
compared in the difference of their outcomes:
a.Patient who were managed under both ICP monitoring and adequate CPP management.
b.Patients who were managed under only the ICP monitoring without further application of
CPP management.
c.Patients who were never managed under the above procedures.
3.Follow up the target population with their survival outcomes and HRQL.
comparison will also be carried out.
Assessment and
4.Interview with neurosurgeon about their experience in CPP management and thus, current
status of surgeon’s acknowledgement and actual performance (from chart review) can be
evaluated.
5.In the middle of the study period, symposiums and lectures will be held to educate the
neurosurgeons regarding the knowledge of “Guideline of Management in Severe Head Injury.”
6.After the promotion period, assessment of the effectiveness of promotion will be performed
base on the proportion change in the institutions that practice the ICP monitoring and CPP
management.
The purposes of the proposal are:
1. To continue the long-term data registry of head injury in Taiwan and thus, to further
identify the severe head injury population for quality-adjusted survival time assessment.
2. To understand the current status of the implication of “Guidelines of Management in
Severe Head Injury” involving the management with adequate cerebral perfusion
pressure (CPP) among major heath institutions in Taiwan.
3. To investigate the outcome difference [Glasgow Outcome Scale (GOS), survival
analysis and Health-related Quality Of Life (HRQL)] among patients with severe head
injury (Glasgow Comma Scale (GCS)≦ 8) after the application of intracranial pressure
(ICP) monitoring and adequate CPP-based management in Taiwan.
4. To improve the outcomes of severe head injured patients in national health via the
promotion of “Guidelines of Management in Severe Head Injury” and re-education of
neurosurgeons.
5. To re-evaluate the effectiveness of education after providing lectures and symposium
for neurosurgeons regarding the use of “Guidelines of Management in Severe Head
Injury.”
Specific Aims
1. Continuously monitoring secular trends of head injury while focused on aims to construct a
first population base study in Taiwan to understand status of current implication and to access
the difference of outcomes in relating to management of adequate CPP.
2. Resolve the controversy over the issue of CPP management between the “right wing” and
“left wing” parties of neurosurgeons in Taiwan. Like Western Countries, our research will
hopefully bring the revolution into neurosurgical field, especially in intensive care procedure
of head injured patients.
3. Through the promotion and education of neurosurgeons the use of “Guidelines of
Management in Severe Head Injury,” we wish to obtain similar mortality rate (34%) as
demonstrated by Western scholars among patients with severe head injury (GCS≦8).
4. Base on literature reviews from Medline, our research may be the first population base study
globally on how the ICP monitoring and adequate CPP management can help to preserve the
HRQL of patients with severe head injury.
Background and Significance
Ever since 1970’s1, a large body of publications has reported that significant reduction in
mortality and morbidity can be achieved by using intensive management protocols.2.3.4 The
protocols emphasized early intubation, rapid transportation to an appropriate trauma care facility,
accurate diagnosis, prompt resuscitation, immediate evacuation of mass lesion if necessary, and
followed by meticulous management in an intensive care unit (ICU) setting. Of the recent
protocol “Guideline of management in severe head injury” developed by both the American
Association of Neurological Surgeons and The Brain Trauma Foundation since 1995, intensive
monitoring of intracranial pressure (ICP)5.6.7 is essential in determining the adequate cerebral
perfusion pressure (CPP)8 and thus, salvage the swelling brain from further ischemia. In the
U.S. a Traumatic Coma Data Bank was purposely set up for the assessment of outcomes of these
neurosurgical protocols. Compared to early studies of 50% mortality,9 the results of efforts in
investigating the proper procedures among each stages, from the incidence of impact to the
moment of discharge, reveals a reduction of mortality rate to average of 36% among severe head
injured patients.10
Among these major discussions, a controversial issue proposed by Rosner in the late 1980’s
in determining the protocol of management of severe head injury patients by adequate CPP
management was not only the revolutionary break through in the filed of neurosurgery but more,
ever since then the idea has been challenged by many right wing neurosurgeon and sustained.
The idea of management has specifically emphasized the importance of ICP monitoring in
sustaining adequate CPP and thus, avoid secondary brain damage. In converse, not until the
1995 while more outstanding results have supported the idea, previous management emphasized
the importance in all measures to reduce the ICP regardless of the ICP monitoring, blood
pressure and CPP. These treatments included large dose of mannitol without proper
maintenance of body fluid, the use of hyperventilation in activating the auto-regulation of vessel
constricture, the use of barbiturate to sedate the patients, and the induction of hypothermia.
Controversy has arisen ever since the left wing party lead by Dr. Rosner suggested that CPP
management directs proper therapy to the pressure gradient across the brain rather than to the
isolated ICP. It requires constant assessment of systemic arterial blood pressure (SABP) –
ICP – CPP interactions corresponds to the view that ICP measurement integrates brain swelling,
brain edema, and tissue perfusion. Demonstrated in the series by Muzelaar and his co-workers,
decreases in ICP were frequently observed when CPP was increased while cerebral flow (CBF)
also increased about 46% after induced hypertension.11 Cerebral perfusion pressure therapy is
not isolated from that of ICP: however the effect of many conventional ICP therapies are
transient, potentially toxic, and better used sparingly if not under proper ICP monitoring.12
Conversely, concern over induced systemic hypertension by the right wing neurosurgeons has
been based on fear of worsening cerebral blood volume and “vasogenic” edema. The party
claimed that there was no correlation between cerebral oxygen consumption and CPP, instead
cerebral oxygen consumption manifests linear relationship corresponding to level of
consciousness (measured by comma scale.)10 In the study of Cruz 1996, he demonstrated that
low CBF values were nonischemic, and thereby associated with normal cerebral oxygen
extraction while he also suggested that in Rosner statements, he did not take into account that
measuring of CBF and metabolism were totally independent of those measuring CPP.10
However, as time would tell, eventually more studies have proposed strong evidence links
systemic hypotension with poorer outcomes in head injured patients and the basis of this
association appears to be the absence of adequate CPP.13.14.15.16 While many studies other than
CPP specific research also demonstrated results to support the idea of adequate CPP
management. In the series by Jones, he had pointed out that in early hydrocephalus (one of the
causes that result in elevated ICP), there was a reduction in membrane synthesis (as ilustrated by
the significant decrease in PME). In the progression of hydrocephalus (sustained high ICP),
there were also significant reduction in ATP and PCr, indicating a reduced capacity in energy
metabolism while finally, there were reduction in great number of components such as NAA,
Asp, Glu, Gln, etc. Especially that low concentration of NAA as discussed by Harris,17
indicates the presence of impaired neuronal development or cortical atrophy. Thus, changes in
metabolite concentration with hydrocephalus could be confounded unless allowance is made for
the water content.18 Meantime, a biochemical study by Higashi et al. (1986) on hydrocephalus
adult animals, also showed modest decreases in ATP and PCr in several brain regions, especially
together with substantial decreases in blood flow. Decrease blood flow was further
demonstrated by the study of Hadani in 1997, he proposed the finding that a significant number
of patients develop increased flow velocities compatible with vasospasm in the basilar artery
after severe head injury. This phenomenon may present an additional factor contributing to the
poor outcome of severely head injured patients.19 While earlier studies of severe head injury
focused on the importance of intracranial pressure elevations,20.21 current evidence emphasizes
the importance of the CPP.16
Although the “Guidelines of Management in Severe Head Injury” has been proposed
regarding the importance of ICP monitoring in maintenance of adequate CPP in Western
countries, controversy has been persisted (even now, still a large body of conservative
neurosurgeons who continuously challenge this new trend of management), the striking results
reported from 1970 to the present with ICP-based techniques is how little impact, if any. Their
application seems to have made on outcome to conclude that ICP monitoring is not useful while
their main focus is on all possible procedures to prevent ICP elevation without intensive ICP
monitoring and management of adequate CPP. In comparison, CPP management also has
permissive role in determining the effect one expected from conventional management such as
use of mannitol,11.22.23 barbiturate24 and other therapeutic modalitite. The main difference is not
changing the management procedure but modifying with intensive ICP monitoring. For
example, barbiturate therapy is still most effective when CPP is high and requires immediate
pressure reduction, although it may lower the CPP threshold.25 Mannitol application is a
routine procedure in the “Guidelines of Management in Severe Head Injury” knowing that under
adequate CPP, mannitol can reach maximum effect on ICP reduction as well as through
increasing effects on oxygen delivery.11.22.23.26.27.28
To prove that any therapy or intervention (such as ICP monitoring) reduces mortality rate
of severe head injured patients from 35% to 25% with α of 5% and β of 20% requires sample
size of 349 in each treatment group. In other words, to prove that ICP monitoring reduces
mortality rate would require a prospective randomized study with (698 + 10%) = 768 patients
(10% is to compensate the missing and loss of follow up patients). In Western countries, the
study of this nature has not been fully carried out for the following reasons: 1) ICP monitoring
has become an integral part of the management of severe head injury in virtually all head injury
research centers. Thus, the constructing of control group may be questionable due to the
ethical and moral issues. 2) In the U.S., most trauma centers can enter only about 50 severe head
injury patients into such studies, this would require a multi-center design and take 4-5 years to
complete. An estimate of over US$5 million dollars for such project was based on past
experience.29 On the contrary, in Taiwan, the nature of high rate of traumatic head injury and
the lag of advanced knowledge provide our research group the study environment without such
limitation and problems related to ethical basis issue in the U.S. However, one of the aims of
this research proposal is to catch up with the Modern Western neurosurgical improvements
through education of neurosurgeons in Taiwan. We have also found significant difference in
outcomes (base on GOS) between Rosner data and our previous databank of head injury in
Taiwan (Table 1). Further, for the research purpose, we believe that through CPP management
protocols, the “Guidelines of Management in Severe Head Injury” would reduce not only the
mortality rate but also improve HRQL of the patients, which from our understanding has not
been studied elsewhere.
Table 1. Comparison of patients’ outcome according to admission GCS score
GOS Score
GCS Score & No of Patients (% of Group)
3
4
5
6
7
N
%
N
%
N
%
N
%
N
%
Dr. Rosner
Death
12 (52) 12
Vegetative
1
(4)
1
Severe
2
(9)
3
Moderate
5
(22)
7
Good
3
(13)
7
Databank in Taiwan (1994-1998)
Death
697 (69) 243
Vegetative
63
(6)
26
Severe
55
(5)
34
Moderate
57
(6)
35
Good
140 (14) 88
(40)
(3)
(10)
(23)
(23)
12
1
5
10
7
(35)
(3)
(15)
(29)
(21)
7
1
1
8
28
(16)
(2)
(2)
(18)
(62)
3
0
3
2
16
(12)
(0)
(12)
(8)
(67)
(57)
(6)
(8)
(8)
(21)
186
25
69
51
150
(39)
(5)
(14)
(11)
(31)
160
31
107
96
265
(24)
(5)
(16)
(15)
(40)
108
35
114
109
433
(14)
(4)
(14)
(14)
(54)
There are reasons supporting our belief that of patients who are treated under adequate CPP
management has better HRQL. These are also factors that withheld the belief of adequate CPP
management against arguments from neurosurgeons of conventional treatments. CPP is the
stimulus to which the autoregulatory response of the vasculature occurs.30.31.32 While also been
demonstrated by Fortune, et al., increase in CPP should always result in some degree of increase
in CBF.33 The series by Shalmon and his colleagues reported intact coupling of flow and
metabolism in a series of severe TBI patients (mean GCS score 6.4) in whom CPP was 85 to 90
mm Hg. As the result, CPP therapy can minimize ICP by reducing intracranial blood volume
through autoregulation of vasoconstriction without deficit in oxygenation extraction and through
prevention of cerebral ischemia. Schrader and associates provided evidence to demonstrate
that systemic hypertension is protective in the face of elevated ICP and mass lesion.34.35
Meanwhile, Dr. Drummond and his co-workers also indirectly rendered the support of the idea
that adequate blood flow may preserve neuronal function by demonstrating that infarct size after
permanent middle cerebral artery occlusion and subsequent edema is mitigated by systemic
hypertension. If the neuronal function could be preserved and secondary brain damage be
minimized, we believe that the benefit would show in functional improvements at discharge and
better HRQL later.
Although outcome evaluation has long been proposed and implemented as a necessary
procedure for health service evaluation, it usually focused on mortality or case fatality.36 If the
quality of medical care increases under CPP management, many patients will survive head
injury that previously would have proved to be fatal and thus, it is important to determine the
effect of CPP management on their quality of life because survivors may leave with permanent
physical, emotional, and psychological sequelae requiring intensive and long term
rehabilitation.37
Quality of life refers to the qualitative aspects of recovery and therefore represents the
more subjective, “sociopersonal” aspects of existence.38
Base on WHOQOL-BREF, measures
of quality of life actually conceptualized in multi-dimensional terms and include four domains:
physical, psychological, environmental, and social well-being. However, while death as the
common end point is the same and relatively easy to measure for all kinds of illness, end point
of morbidity or QOL are relatively difficult to define, measure or compare. In this study, we
intend to assess the result of CPP management base on quality adjusted survival time39.40, rather
than to provide only the index of quality of life or only the timing of death. QAST is an
estimator by multiplying the QOL into the survival function, which can be used in outcome
evaluation.
Research Designs and Methods
This proposal is designed for the study, which will include the period from January 1, 2002 to
December 31, 2006. Our research proposal has its intention to collect data of head injury
casualty cascade from four quadrants of Taiwan such as North, South, East and West. Data
from four major areas will be collected to represent each quadrant of Taiwan geographically.
Taipei City was selected to represent urban northern part of Taiwan. Hualien County
represents rural eastern part of Taiwan. Taichung City and Taichung County represent central
western part of Taiwan and finally, Kaoshong City and Kaoshong County represents southern
part of Taiwan.
Study Area
Taipei, the center of economy, politics and cultural activities of Taiwan, faces a serious
mass-transportation system problem. The government is already on the process of solving this
dilemma. The mass rapid transit system, touted as the solution to this problem, has been
completed in the turn of century. But the system only covers few major sites recently. A
substantial number of people still rely on motorcycles, buses and cars, particularly the former, as
their means of transportation. The total population in Taipei in 1999 was 2,641,312, males
numbering 1,309,434 and females numbering 1,331,878.
Most of head injury cases end up in the emergency rooms of large-sized teaching hospitals
in Taipei. Some cases are referred from medium- or small-sized hospitals, where very few
operations are performed. All cases of head injuries from 19 medium and large-sized hospitals
in Taipei City will be collected.
Taichung county and its heart, Taichung City, a newly developed metropolitan area with
well-organized city plan, represent the central geographical quadrant of Taiwan. Because of its
excellent city construction, Taichung does not face the mass-transportation issues like Taipei,
however, its medical facilities are not as abundant as Taipei. The total population in 1999 was
2,421,996, males 1,226,514, and females 1,195,482. Motorcycles are the primary choice of
transportation in this area and head injury cases will be collected from 13 major hospitals in
Taichung.
In 1999, Kaoshong City and Kaoshong County have total population of 2,705,857 which is
also the largest city in the east coast, geographically. Out of its total population, there are
1,386,376 males and 1,319,481 females. Head injury cases will be collected from 13 major
hospitals in the area.
Hualien County, the largest administrative unit in the eastern Taiwan, includes as many as
fifteen cities and towns. The total population in 1999 is 355,686, males 188,587, females
167,099. Four large-scale hospitals provide emergency care to head-injured patients in Hualien
County. Tsu-Chi Hospital is the tertiary referral hospital in the area; another 3 hospitals were
also equipped to perform emergency craniotomy on head-injured patients, and all head injury
cases.
Subjects
Medical centers were selected according to two criterias: having 100 beds inpatient facility
and neurosurgery department. Head injuries were often treated in the medical centers though
sometimes small and middle-sized hospitals also had head injured patients, who were often
transferred to medical centers for treatment. The ICD-9 Classification Code was used to
determine the clinical cases. Head-injured patient was defined as one who, after having
received direct or indirect injury of head, exhibits obvious brain concussion, contusion, skull
fracture or any of the clinical manifestations of skull fractures and ICH. GCS was first
determined regarding the severity of patients during admission in emergency department.
Followed up clinical manifestations may persist or deteriorate, which included loss of
consciousness, amnesia, neurological deficit, and seizures. Since only hospital inpatients and
death during hospitalization are registered; therefore, the recordings do not include non-hospital
death such as death on-arrival at the hospital. In general, a patient with one or more of the
fore-mentioned symptoms or diagnoses was registered as a head-injured patient, and their
treatment and recovery outcomes were also recorded.
Definition
The classification by Kraus et al. was adopted to grade the degree of head injuries, such as
brain concussion, skull bone fracture, brain damage with clear neurological deficit and clinically
observable cognitive deficit, post traumatic amnesia, neurological sequelae and any evidence of
intracerebral hemorrhage. Presence of any one of the above conditions confirmed the
diagnosis of head injury in the registry.
A. Glasgow Coma Scale (GCS) was used to categorize the severity of head injury.
a). Severe: GCS score below 8.
b). Moderate: GCS score between 9 and 12. Patient underwent neurological operations. or
had abnormal computerized tomographic findings of the brain.
c). Mild: Conditions not described above.
B. Glasgow Outcome Scale (GOS) - extension version was used to categorize the outcome of
patients after hospital discharge.
a). Death.
b). Vegetative state.
c). Severe disability – conscious but requiring 24-hour care.
d). Moderate disability – disabled but having the ability of self-care.
e). Good clinical recovery.
Data Registry Procedures
Data will be collected form the 49 health institutions within four major geographical
domains of Taiwan. Through the assistance of Taiwan Neurosurgery Association and
Injury Prevention Association,R.O.C., we may reach a common consensus with these
health institutions and most of the neurosurgeons. With the assistance of physicians and
nurses in the Neurosurgery Department, new admission cases of head injury can be
followed up weekly by either hand-written questionnaire or disk-contained file. While
they will also be well informed and trained through lectures regarding the important items of the
questionnaire (or file) and selection of the cases. From the review of medical charts, head
injury cases were selected and non-resident patients were excluded from the present study.
Data registry involved the following procedures:
1.
For non-fatal cases, admission records and hospital charts of all the studied hospitals were
reviewed.
2.
Medical charts were reviewed for identification of fatal cases and ICD-9 codes were also
employed to identify cases. A final list of 9 ICD rubrics of diagnoses was adopted (Table
5). The hospital chart of each potential case as obtained from the ICD rubrics was
examined to determine if evidence of head injury was noted and if the above criteria were
met.
Table 5. ICD-9 Coding Description
Rubric NO.
800
801
803
804
850
851
852
853
854
Description
Fractured vault of skull
Fractured base of skull
Other unqualified skull fracture
Multiple fracture skull/face
Cerebral concussion
Cerebral laceration and contusion
Subdural, subarachnoid, extradural hemorrhage
Other and unspecified intracranial hemorrhage
Intracranial injury: other unspecified
3.
Additional information from the medical chart review regarding the ICP monitoring and
adequate CPP management such as ICP measurement, volume of cerebrospinal fluid
drainage, volume of intakes, volume of outputs, measurement of blood pressure, daily dose
of mannitol treatment, daily dose of barbiturate treatment, presence of hyperventilation
treatment, and presence of vasopressor treatment will also be specifically noted. The
interviewers are only responsible for recording data but not to categorize the cases.
The criteria for the categorization will only be determined by our research team and
all the cases can be then categorized into the following three groups when data analysis
is processing:
a.
Patient who were managed under both ICP monitoring and adequate CPP
management.
b.
Patients who were managed under only the ICP monitoring without further
application of CPP management.
c. Patients who were never managed under the above procedures.
4.
Through the data collection from these 49 health institutions, comparison of the effect
of the protocol would be made within and between hospitals. Severe cases who
admitted to institutions and have not been carried out of ICP monitoring nor CPP
management will be our control group.
5.
To develop the WHOQOL-BREF of Head Injury – Taiwan version, a HRQoL
committee will then be organized to review trauma-related references, test the
internal and external validity and reliability by experts and focus groups.
6.
After receiving the weekly registry from data collectors, research personnel will select the
cases of severe ones (GCS≦8) and follow up with surveillance of their HRQL and survival
status. The measurement of HRQL is base on the WHOQOL-BREF – Taiwan
Version.59.60.61 Follow up will be carried out for every 3, 6, and 12 months according to
patients’ admission date.
7.
In the third, fourth, and fifth year, the objective will focus on the promotion of the
new protocol and re-education of neurosurgeons. Workshop will be held in the
beginning of the third year to discuss the result from previous years and symposiums
will be held throughout the year nationwide. We wish to broadcast the information
to nationwide health institutions under the assistance of Neurosurgery Association
and Injury Prevention and Control Association.
8.
The purposes of interviewing with neurosurgeons are to evaluate the difference of
their perception and practice when taking care of TBI patients, and to obtain the
percentage of adherence to the CPP management in our country. To reach these two
purposes, a questionnaire must be developed and tested for its validity before it is
adopted.
Time-Table
As previously addressed, to prove that any therapy or intervention (such as ICP monitoring)
improves mortality of severe head injured patients from 35% to 25% with an alpha of 5% and
beta of 20% requires sample size of 349 in each treatment group. From the traumatic head
injury databank in 1999, we have obtained about 600 severe cases and among them, an
estimation of 40% of patients assume to be treated under the ICP monitoring. However, of the
240 ICP monitoring cases, less than 60% of patients were actually treated with the “Guideline of
Management in Severe Head Injury” involving adequate CPP management. Thus, data registry
for minimum of two-years is necessary to obtain substantial number of population for statistical
significance. The details of proposed time schedule among the 5 years of study period is as
followed:
The First Year
In the first year, data will be coded and basic analysis will be done on a weekly basis.
Evaluations of the project will be made periodically. GOS will be extracted from the discharge
note. Follow up interview with severe head injured patients about their HRQL will be carried
out independently at 3, 6, 12 months after the admission date. Meanwhile, we will do
additional evaluation on information related to head injury management and prevention such as
assessment of risk factors among minor head injury, of trend of head injury among the bicycle
riders, and of relative increase in associated injuries of motorcyclist. During the last 2 months
of the year, we will re-examine the whole study and calculate the quality-adjusted survival time.
Following formula will be inquired for obtaining the quality-adjusted survival time in the time
interval (ti, ti+1):
QSi = [ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2 + S(ti+1) * [ qol(ti) + qol(ti+1) ]/2
Details will be further addressed in analysis section. Eventually, we will write a report on the
difficulties and task limits found during the course of the study and on the completeness of the
registry.
The Second Year
In the second year, continuation of data registry will be collected while we will also modify
the study according to the recommendations of the report written at the end of the previous year
in order to reduce labor and increase the usefulness of the collected data. Base on the
information related to ICP monitoring and CPP management, the ratio of institutions who has
currently practiced the “Guidelines of Management in Severe Head Injury” (the Guidelines) will
be estimated from the data obtained (current status of implication). Meanwhile interviews with
neurosurgeons will base on the designed questionnaire used to identify the acknowledgement of
the Guidelines among neurosurgeons (ideal status of implication). Questionnaire will be
designed under the assistance from Dr. Sheng-Jean Huang, Shin-Yuan Chen, and Jia-Wei Lin.
From the assessment of the status and ratio of institutions performing management base on
the Guidelines, it will provide essential information for adjustment of the collecting period to
obtained statistical significant number of population. Constant periodic evaluation of the
project will also be made. At last two months of the second year, preparation of symposium
related to management under the Guidelines will be promoted through the help from major
governmental division or private sectors. Our project result, summary of international study,
and protocols practiced in western countries will be demonstrated in the Symposium. Scholars
from abroad will also be invited in addition to the domestic speakers. The Symposium will be
carried over to the third year.
The Third Year
The major focus during this year will be pushing the implication of the Guidelines through
the proper channel or promotion. Major expense will be the preparation of Conference and
Symposium. Meantime under the condition of inadequate amount of statistical significant
population, we will continue the data registry and assessment of HRQL of the severe injured
patients. Additional study on the possible risk factors and complications associated with the
ICP monitoring will also be done during the year.
The Fourth Year
In this year, procedure will be carried out similar to the first year. Evaluation of the
effectiveness of the promotion will be constructed based on the assessment of records associated
with ICP monitoring and CPP management which are collected from the same health institutions.
Investigation of the surgical outcomes and quality adjusted survival time will also be routinely
carried out to demonstrate possible improvements in patients’ outcomes. Base on the
promotion of the Guidelines involving adequate CPP management, we expect a shorter duration
of collecting period because of the increasing use of CPP management, and the adjustments of
collecting period will be done.
The Fifth Year
Similar procedures as the second year will be done in the beginning of the year. The
analysis of effectiveness of promotion (base on both interviews with neurosurgeons and data
assessment) is expected for completeness by the middle of the year. Under permitted time and
funding, we intend to design a research relating to cost-utility analysis, and propose a proper set
of guidelines that is suitable for medical environment in Taiwan.
The First Year
Time-Table for Study
Tasks
1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon
Data Registry
Survival &
HRQL Follow Up
Coding
Data Analysis
Project Re-examination
Periodic Evaluation
Report
The Second Year
Time-Table for Study
Tasks
1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon
Data Registry
Survival &
HRQL Follow Up
Preparation for Symposiums
Interview w/ Neurosurgeons
Basic Analysis
Implication Status Analysis
Project Re-examination
Periodic Evaluation
Report
The Third Year
Time-Table for Study
Tasks
Data Registry
HRQL Follow Up
Promotion & Education
Basic Analysis
Periodic Evaluation
Report
1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon
The Fourth Year
Time-Table for Study
Tasks
1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon
Modify Research Method
Data Registry
HRQL Follow Up
Data Analysis
Advanced Analysis
Project Re-examination
Periodic Evaluation
Report
The Fifth Year
Time-Table for Study
Tasks
Data Registry
HRQL Follow Up
Interview w/ Neurosurgeons
Data Analysis
Outcome Analysis
Cost-Utility Analysis
Project Re-examination
Periodic Evaluation
Report
1-2Mon 3-4Mon 5-6Mon 7-8Mon 9-10Mon 11-12Mon
Analysis
Current methods of estimating quality adjusted life year include the follows: quality
adjusted life-year (QALY) approach by Torrance, the disability adjusted life-year (DALY)
approach by Murray, quality adjusted survival estimation with partitioned survival approach by
Glasziou, and the quality adjusted survival time (QAST) approach by Hwang38. After careful
review, the recent method of QAST by Hwang is the choice of approaches by our research team
in obtaining quality-adjusted life year among patients who suffered severe head injury.
QSi = [ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2 + S(ti+1) * [ qol(ti) + qol(ti+1) ]/2
QAS =Sum [qasc(tk│x)(tk+1 - tk) ]
= Sum { [ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2}(tk+1-tk)
In the above formula demonstrated by Hwang (quality adjusted survival time, second
paper), where, S(ti) equal survival probability at time ti and qol(ti) equal mean health-related
quality of life at time ti. The first term, “[ S(ti) – S(ti+1) ] / 2 * [ qol(ti) – qol(ti+1) ] / 2”
corresponds to the quality adjusted survival portion contributed by patients who died in the
period of (ti, ti+1) and second term derived from patients who still survive at ti+1. The expected
QAST can be calculated by multiplying the HRQL into the survival function at the point of time
when the HRQL is measured (3,6 and 12 months after admission).
Current status of application of management involving adequate CPP will be determined by
the proportion of health institutions whom information of ICP and CPP related records shows
adequate measurement: presence of ICP measurement, intake is averaged 6000 cc per day,
output is averaged 6000 cc per day, and mannitol is averaged 160 g per day. However the
standard are not absolute, the measurements are confounding by many other factors such as
underlying disease. The ideal status will be determined by the proportion of surgeons who
demonstrate sufficient knowledge related to “Guidelines of Management in Severe Head
Injury.” Questionnaire will be scored base on the consultation from our co-investigators who
has proficient knowledge in either the neurosurgical fields or CPP management.
DBASE, SPSS 10.1 and S plus software will be used as the data management system.
The demographic data, cases of injury, neurological manifestation, severity, imagine diagnosis,
treatment and outcome will first be analyzed in addition to our purpose of proposal. The
severe head injured patients of the 3 non-overlapping groups, which was categorized base on the
presence of ICP monitoring and CPP management will be further assessed on the likelihood
ratio 2 test and ANOVA to evaluate the difference of the outcomes (GOS). Meanwhile,
survival analysis will also be used to assess the HRQL and thus, compare the differences
between each subgroup. Regression model is to identify possible risk factors associated with
the new management. The differences are considered statistically significant if the p value is
less then 0.05, and having significant trend if the p value is between 0.05 and 0.01..
After collection of data, database will be sent to School of Public Health, Taipei Medical
University, and Department of Physical Therapy, National Taiwan University for data analysis.
Prof. Hung Yi, Chiou, Jau-Yih Tsauo, and Maou-Rong Lin, investigators who have outstanding
reputation in both fields of epidemiology and biostatistics, and survival analysis will assist our
research team for further assessment.
Anticipated Results
From this study, we hope to obtained the following results:
1. Evidence to prove the outstanding result in improvements of outcome among the institutions
whom severe head injured patients were managed under close ICP monitoring and
maintenance of adequate CPP.
2. Through further education and promotion, we hope to bring the new concept into the
neurosurgical field of Taiwan to reduce mortality rate in head injury cases.
3. Provide first assessment relating to the improvements in quality-adjusted survival time
among patients who were treated with the “Guidelines of Management in Severe Head Injury.”
4. Provide information needed for future research in constructing an appropriate new
neurosurgical guidelines base on cost-utility analysis suitable to National Health Insurance
System in Taiwan. Also, a disease specific RQL quotes related to head injury can be
designed in the future base on the information obtained and more precise assessment can be
performed in quality of life among head injured patients.
5. Like the traumatic center databank (TCDB) in U.S, most of our studies will serve as
references for the implementation of the prevention strategies by the government, and for the
research among scholars.
6. There is difficulty in obtaining sufficient number of prospective cases for most accurate
statistical assessment. Unlike U.S., our problem is to find cases under this modern
management. Thus, uncertainty in collection period is our major concern.