British Journal of Neurosurgery

ISSN: 0268-8697 (Print) 1360-046X (Online) Journal homepage: http://www.tandfonline.com/loi/ibjn20

Comparison of early and late decompressive

craniectomy on the long-term outcome in patients
with moderate and severe traumatic brain injury:
a meta-analysis

Kai Zhang, Wenjie Jiang, Tieliang Ma & Haorong Wu

To cite this article: Kai Zhang, Wenjie Jiang, Tieliang Ma & Haorong Wu (2016) Comparison of
early and late decompressive craniectomy on the long-term outcome in patients with moderate and
severe traumatic brain injury: a meta-analysis, British Journal of Neurosurgery, 30:2, 251-257, DOI:
10.3109/02688697.2016.1139052
To link to this article: https://doi.org/10.3109/02688697.2016.1139052

Published online: 01 Feb 2016.

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BRITISH JOURNAL OF NEUROSURGERY, 2016
VOL. 30, NO. 2, 251–257
http://dx.doi.org/10.3109/02688697.2016.1139052

ORIGINAL ARTICLE

Comparison of early and late decompressive craniectomy on the long-term outcome

in patients with moderate and severe traumatic brain injury: a meta-analysis
Kai Zhanga,b*, Wenjie Jiangc*, Tieliang Mad and Haorong Wua
a
Department of General Surgery, the Second Affiliated Hospital of Soochow University, Soochow, Jiangsu, P.R. China; bDepartment of Hepatobiliary
Surgery, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, P.R. China; cDepartment of Anesthesiology, the Affiliated Yixing Hospital
of Jiangsu University, Yixing, Jiangsu, P.R. China; dCentral Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, P.R. China

ABSTRACT ARTICLE HISTORY

Background Several studies have searched whether early decompressive craniectomy (DC) can improve the Received 27 February 2015
long-term outcome of patients with moderate and severe traumatic brain injury (TBI). However, the effects of Accepted 3 January 2016
early DC remain unclear. The purpose of this meta-analysis was to assess whether early DC (time to surgery Published online 28 January
after injury524 h) is better than late DC (424 h) after moderate and severe TBI. Method Two reviewers 2016
independently searched Pubmed, Embase, ISI web of science, the Cochrane Library and Scopus databases KEYWORDS
from inception to 4 November 2014. Studies comparing the long-term outcome of patients following early Decompressive craniectomy;
and late DC after TBI were included. The long-term outcomes were evaluated by Glasgow Outcome Score, meta-analysis; outcome;
Extended Glasgow Outcome Score. Newcastle-Ottawa Scale was used to assess the methodological quality traumatic brain injury
of included studies. Characteristics of the selected studies were extracted. Pooled results were presented by
odds ratios (ORs) with 95% CIs. I2 was used to test heterogeneity. Pearson correlation coefficient was used to
detect the relationship between bilateral pupil abnormality and unfavourable outcome. Results Five articles
were eligible for this meta-analysis. The pooled results of comparison of unfavourable outcome and
mortality revealed no significant difference in the early and late groups (ORs: 1.469; 95% CIs: 0.495–4.362;
p40.05; I2 ¼ 70.5% and ORs: 1.262; 95% CIs: 0.385–4.137; p40.05; I2 ¼ 77.6%, respectively). Pearson
correlation coefficient indicated that bilateral pupil abnormality was positive related to the unfavourable
outcomes and mortality (r ¼ 0.833; p50.05) (0.829; p50.05). Conclusion Bilateral pupil abnormality is
positive related to unfavourable outcome and mortality in the patients following DC after moderate and
severe TBI. Early DC may be more helpful to improve the long-term outcome of patients with refractory
raised intracranial cerebral pressure after moderate and severe TBI. However, more RCTs with better control
of patients with bilateral pupil abnormality divided into the early and late groups are needed in the future.

Introduction assess whether early DC could improve the long-term outcome of

Traumatic brain injury (TBI) is a major cause of morbidity and
mortality worldwide, especially among young adults. 1 In the USA,
approximately 2% of the population is affected by TBI, resulting
in 235,000 hospitalisations and 50,000 deaths, which causes
enormous financial burden to the society and family. 2 Raised
intracranial cerebral pressure (ICP) is a severe complication after
TBI due to mass lesions, haemorrhage or diffuse cerebral oedema.
Uncontrolled intracranial hypertension can cause cerebral ische-
mia and further secondary insults through lower cerebral
perfusion pressure.3,4
Decompressive craniectomy (DC) plays an important role in the
management of raised ICP refractory to the conservative treatments
after TBI. Several studies have proved that DC can reduce ICP
effectively.5 However, DC is always used as a second tier, perhaps
even a last-ditch management for its high complication rates and
unclear long-term outcome.6–9
Recently, a number of studies have researched the impact of
performing DC as a first tier treatment in patients with TBI and the
results were variable. Therefore, we conducted the meta-analysis to
patients after TBI.
Methods
Search strategy and selection criteria
Two investigators (Z.K. and J.W.J.) independently searched
Pubmed, Embase, ISI web of science, the Cochrane Library and
Scopus databases between inception and 4 November 2014 for
studies that compare the long-term outcome of patients following
early and late DC after TBI. The medical subject heading terms
were ‘traumatic brain injury’ and ‘decompressive craniectomy’ and
‘outcome’.
Studies were included if they met the following criteria: (1)
Cohort and randomised controlled trial (RCT) compared the long-
term outcomes of patients separately receiving early (time to surgery
after injury ≤ 24 h) and late DC (424 h) after TBI; (2) Preoperative
Glasgow Coma Scale (GCS)≤ 12; (3) Preoperative ICP ≤25 mmHg;
(4) All patients were treated from admission according to the
guideline for head injury management; (5) The long-term outcome

CONTACT Haorong Wu 2726562302@qq.com The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Soochow, Jiangsu 215004, P.R. China
*These authors are contributed equally

© 2016 Taylor & Francis

252 K. ZHANG ET AL.
was evaluated by Glasgow Outcome Score (GOS)10 or Extended
Glasgow Outcome Score (GOSE)11. Exclusion criteria were as
follows: (1) Patients younger than 15 years or older than 70 years.
(2) Studies were not written in English; (3) Patients with other types
of injury can affect the outcome; (4)The follow-up time 53 months;
(4) Case reports, expert opinions, letters and reviews.
If agreements could not be reached, they were resolved by a third
investigator (M.T.L.). Electronic mails would be sent to the authors
of the selected studies for additional data which is not available in
their articles. If no response was received, the study was excluded.
Methodological quality of included studies
The Newcastle-Ottawa Scale (NOS)12 was used to assess the
methodological quality of the included studies based on their
selection of participants, comparability of groups and exposure/
outcome ascertainment. A total score of 6 or greater (maximum
score, 8) was used to identify higher-quality studies.
Data extraction
Following data were extracted from the selected studies: first author;
year of publication; region; study design; number of patients; male
rate; age; preoperative GCS; preoperative ICP; pupils reactivity;
Marshall’s classification; surgical technique; time to surgery after
injury; follow-up time; complications; outcome (GOS; GOSE;
mortality). We assumed favourable outcome as GOS: 4–5; GOSE:
5–8 and unfavourable outcome as GOS: 1–3; GOSE: 1–4.
Statistical analysis
Statistical analyses were performed using STATA version 12 (Stata
Corp., College Station, TX). The pooled results of comparison of
long-term outcome following early and late DC after TBI were
Figure 1. Identification process for eligible studies. Study selection. *Among the 1587 studies, most were not relevant to the theme, such as researched other kinds of brain
diseases or not use DC as a treatment method, the rest were about the children or infants.
expressed as odds ratios (ORs)13 with 95% confidence intervals
(CIs). Heterogeneity among included studies was assessed using the
Cochrane Q statistic and qualified with the I2 lying between 0% and
100%, I2450% showed that heterogeneity among studies produce
some impact, which case the random effects model was applied,
whereas analyses were performed with a fixed effects model if I2
was 550%, which indicated that homogeneity was good for the
reliability of meta-analysis.14 Influence analysis and subgroup
analysis would be conducted to investigate the potential sources
of heterogeneity and found out the characteristics of including
patients which could affect the long-term outcomes.15 All statistical
tests were two sided, with p values50.05 demonstrating statistical
significance.
Results
Study identification and selection
The literature search was performed as described, and 1685
potentially relevant studies were identified. After reviewing the
titles and abstracts, 1587 articles were excluded. In the 1587 studies,
most were not relevant to the theme, such as researched other kinds
of brain diseases or not used DC as a treatment method, the rest
were about the children or infants. After a full-text review, further
93 studies were excluded and only 5 articles16–20 were eligible for the
current meta-analysis. In the 93 studies, including 40 other forms of
articles, 33 not researched the long-term outcome of DC, 17 not
compared the early and late DC and 3 meta-analysis (Figure 1).
Characteristics and quality of the included studies
Two hundred and eighty-two patients with moderate and severe TBI
were included in this analysis, 153 of them accepted early DC and
129 with late DC. The study samples ranged from 40 to 76. The
included patients were all young adults and the ages ranged from
Table 1. Characteristic of included studies in comparison of the long-term outcome following early and late DC after moderate and severe TBI.
Follow-up
time
Study/year Region Study design Operation procedure Characteristics of the included patients (months) Main outcome (patients)
Wen et al. (2011) 16
China Prospective cohort Large uni/bifrototemporoparietal Early group: 1. 25 patients (17 males); 2. Age: 6 Early group: GOS 4–5: 13, GOS 1–3: 12;
surgery 46.7 ± 13.3 years; 3. GCS: 6 ± 1.9; 4. Pupillary Mortality: 5/25. Late group: GOS 4–5: 12,
abnormality: 17 one side or none, 8 both sides; 5. GOS 1–3: 7; Mortality: 4/19
Marshall’s classification: 8 IV, 17 V; 6. Time to
surgery after injury: 8.0 ± 4.9 h. Late group: 1. 19
patients (15 males); 2. Age: 50.2 ± 15.5; 3. GCS:
6.6 ± 2.5; 4. Pupillary abnormality: 14 one side or
none, 5 both sides; 5. Marshall’s classification: 3 IV,
13 V; 6. Time to surgery after injury: 3.2 ± 1.8 days
Albanese et al. (2003)17 France Prospective cohort Large uni/bifrototemporoparietal Early group: 1. 27 patients (24 males); 2. Age: 35 ± 15 12 Early group: GOS 4–5: 5, GOS 1–3: 22;
surgery years; 3. GCS: 5 ± 2; 4. Pupillary abnormality: 12 Mortality: 14/27. Late group: GOS 4–5: 5,
one side, 15 both sides; 5. Time to surgery after GOS 1–3: 8; Mortality: 3/13
injury:524 h. Late group: 1. 13 patients (9 males);
2. Age: 27 ± 15 years; 3. GCS: 5 ± 3; 4. Pupillary
abnormality: 7 one side, 6 both sides; 5. Time to
surgery after injury:424 h
Sonuca (2010)18 Turkey Retrospective cohort Large uni/bifrototemporoparietal Early group: 1. 40 patients (24 males); 2. Age: 12 Early group: GOS 4–5: 20, GOS 1–3: 20;
surgery 41.3 ± 17.2 years; 3. GCS: 6.4 ± 1.3; 4. Time to Mortality: 5/40. Late group: GOS 4–5: 10,
surgery after injury: 4.3 ± 1.5 h. Late group: 1.36 GOS 1–3: 26; Mortality: 16/36
patients (21 males); 2. Age: 37.6 ± 18.4 years; 3.
GCS: 6.2 ± 1.2; 4. Time to surgery after injury:
35.7 ± 5.6 h
Cianchi et al. (2012)19 Italy Retrospective cohort NA Early group: 1. 41 patients (29 males); 2. Age: 6 Early group: GOS: 3.3 ± 1.4 scores; Mortality:
43.8 ± 17.9 years; 3. GCS: 7.1 ± 3.5; 4. Marshall 20/41. Late group: GOS: 3 ± 1.1 scores;
score: 3.2 ± 0.8; 5. Time to surgery after Mortality: 9/21
injury:524 h. Late group: 1. 21 patients (16 males);
2. Age: 35.7 ± 19.4 years; 3. GCS: 7.2 ± 3; 4. Marshall
score: 2.4 ± 0.8; 5. Time to surgery after
injury:424 h.

BRITISH JOURNAL OF NEUROSURGERY

Gouello et al. (2014)20 France Retrospective cohort
GCS: Glasgow Coma Scale; GOS: Glasgow Outcome Score; NA; not available.
Large uni/bifrototemporoparietal Early group: 1. 20 patients (15 males); 2. Age: 33.5 24 Early group: GOS 4–5: 6, GOS 1–3: 14;
surgery years; 3. GCS: 7.25; 4. Pupillary abnormality: 13 one Mortality: 10/20. Late group: GOS 4–5: 24,
side or none, 7 both sides; 5. Marshall’s classifica- GOS 1–3: 16; Mortality: 7/40
tion: 4 IV, 16 V; 6. Time to surgery after injury:
13.2 h. Late group: 1. 40 patients (31 males); 2.
Age: 31.5 years; 3. GCS: 7.22; 4. Pupillary abnor-
mality: 34 one side or none, 6 both sides; 5.
Marshall’s classification: 26 I + I, 14 III + IV; 6. Time
to surgery after injury: 2.35 days

253
254 K. ZHANG ET AL.
Figure 2. NOS of included studies.
Figure 3. Pooled OR of unfavourable outcome.
30 to 50 years. Four of the included studies 17–20 with preoperative
GCS58, which meant the including patients suffered severe TBI.
All of the selected studies used cohort design, three with
retrospective18–20 and two with prospective16,17. Three studies16,17,20
described the pupil reactivity of the including patients separately in
the two groups in detail and one study18 excluded patients with
bilateral fixed and dilated pupils. The bilateral pupil abnormality
rates were higher in the early DC group than in the late DC group in
three studies. The operation methods in four studies were all large
unilateral or bilateral frototemporoparietal craniectomy and not
mentioned in one study (Table 1). The timing when to execute DC
was based on the computed tomography (CT) findings and ICP in
all five studies. Early DC would be taken when the CT scan at
admission showed a severe midline shift (45 mm) or compression of
the cisterna ambiens. If the ICP was persistently high and was
refractory to medical treatment, then late DC would be used.
Methodological quality of included studies
The scores of included studies ranged from 7 to 8, with a minimum
of 8 according to the NOS. One study showed that low quality in the
comparability of cohorts on the design for the patients with pupil
abnormality was significantly different in the two groups.20
 BRITISH JOURNAL OF NEUROSURGERY 255

Figure 4. Pooled OR of mortality.

Table 2. Subgroup analyses for the potential factors which could influence the outcome.
No. of Unfavourable No. of
studies outcome (95% CI) p Value I2 studies Mortality (95% CI) p Value I2
Study design
Prospective 2 1.978 [0.772; 5.068] 40.05 0% 2 1.824 [0.489; 6.806] 40.05 36.40%
Retrospective 2 1.133 [0.130; 9.867] 40.05 88.10% 3 1.018 [0.166; 6.241] 40.05 87%
Preoperative GCS
GCS512 1 1.582 [0.468; 5.351] 40.05 – 1 0.938 [0.214; 4.100] 40.05 –
GCS ≤ 8 3 1.469 [0.321; 6.718] 40.05 80% 4 1.360 [0.312; 5.932] 40.05 83.10%
Follow-up time
6 months 1 1.582 [0.468; 5.351] 40.05 – 2 1.145 [0.484; 2.708] 40.05 0%
12 months 2 0.945 [0.138; 6.451] 40.05 79.10% 2 0.769 [0.041; 14.58] 40.05 89.80%
24 months 1 3.500 [1.112; 11.01] 40.05 – 1 4.714 [1.424; 15.60] 50.05 –

All selected studies had high quality according to the assessment
criteria (Figure 2).
Main outcome
Four included studies16–18,20 provided the specific numbers of
patients suffered favourable or unfavourable outcome separately
in the early DC group and late DC group and the pooled result
revealed no significant difference between the early and late DC
groups (ORs: 1.469; 95% CIs: 0.495–4.362; p40.05) (Figure 3).
Five studies reported the mortality separately in the early DC
and late DC groups and the pooled result showed also no
significant difference between the early and late DC groups (ORs:
1.262; 95% CIs: 0.385–4.137; p40.05) (Figure 4).
However, significant heterogeneity existed both in the unfavour-
able outcome and mortality analyses (I2 ¼70.5%; I2 ¼77.6%,
respectively). Then, we performed the influence analysis
and found the Sonuca study18 influence the result of unfavour-
able outcome significantly. A sub-analysis including other three
studies16,17,20 was performed, the result indicated less unfavour-
able outcomes in the late DC group than early DC group (ORs:
2.489; 95% CIs: 1.203–5.150; p50.05; I2 0%). ¼ Subgroup
analyses of study design, preoperative GCS and follow-up
time were performed, no important findings were detected
(Table 2).
Influence of pupil reactivity to the long-term outcome
We found the Sonuca study18, which impact the pooled results
significantly exclude the patients with bilateral dilated and fixed
pupils. Therefore, we performed Pearson correlation analyses of
pupil reactivity, unfavourable outcomes and mortality, and the result
indicated bilateral pupil abnormality was positive related to the
unfavourable outcomes and mortality (r ¼ 0.833; p50.05) (0.829;
p50.05) (Figure 5).
Discussion
DC used as a surgical technique for decreasing raised ICP has been
used for more than 100 years.21,22 It was always used as a life-saving
procedure for its high complication rate and unclear long-term
outcome in the past. With increased understanding of the patho-
physiology of TBI, several researchers have studied whether early
DC would bring more benefits to the patients and the results were
variable. Recently, the first large prospective RCT conducted by
Cooper et al.23 (DECRA study) indicated that early bifrototempor-
oparietal DC can decrease ICP and the length of stay in the ICU but
associated with more unfavourable outcomes. However, several
researchers held different opinions about this conclusion. For
instance, the median time from injury to randomisation was 37.5 h
in this study. Timmons et al.24 considered this interval was too long
which could affect the result. In another ongoing multicentre study
256 K. ZHANG ET AL.
Figure 5. (A) Relationship between bilateral pupil abnormality and unfavourable
outcome. (B) Relationship between bilateral pupil abnormality and mortality.
(RESCUEicp trial), the criteria were that randomisation of DC or
conservative treatment would begin when the ICP above 25 mmHg
and last 1–12 h, refractory to initial medical measures. Thus, we
performed this meta-analysis to comprehensively evaluate the
results. The main results of our meta-analysis indicated that
performing DC early would not improve the long-term outcome.
The unfavourable outcome rate and mortality were comparable in
early and late DC groups. However, significant heterogeneity existed
among the results. Then, influence analysis and subgroup analyses
were conducted to find the source of heterogeneity. The results
indicated that preoperative bilateral pupil abnormality would
seriously impact the result. Then, we used Pearson correlation
analysis to research the relationship between bilateral pupil abnor-
mality and long-term outcomes and the results showed bilateral
pupil abnormality was significantly positive related to the unfavour-
able outcome and mortality. In the past studies, pupillary dilatation
and absence of reaction to light after injury generally indicated brain
hernia, secondary brain stem injury and was associated with poor
outcome.25–27 Therefore, we considered the result in Sonuca et al.’s
study was more reliable for the study excluded the patients with
bilateral fixed and dilated pupils. In other studies, numbers of
bilateral pupil abnormality patients were significantly different in
the early DC and late DC groups. In the Cooper et al. study, patients
with bilateral pupil abnormalities were also significantly higher in
the DC group than in the control group, so the conclusion proposed
by Cooper et al.23 that early DC associated with more unfavourable
outcomes should be cautious treated. Complications following DC
could not be evaluated for few data that were available from
included studies, but we could speculate that the complication
rates were comparable in the early and late DC groups from the
extracted data.
The meta-analysis had several advantages. First, all the included
patients had similar ages, sex ratio, preoperative GCS, Marshall’s
classification and adopted same operation method between the two
groups. Second, the patients received standard acute treatment
before surgery. Third, no publication bias was detected. Fourth, all
the included studies were written in English. There were also some
limitations in the meta-analysis. First, the study samples were small.
Second, the heterogeneity was significant. Third, all the included
studies were cohort studies.
Conclusion
Bilateral pupil abnormality is associated with unfavourable outcome
and mortality in the patients following DC after moderate and
severe TBI. Early DC may be more helpful to improve the long-term
outcome of patients with refractory raised ICP after moderate and
severe TBI. However, more RCTs with better control of patients
with bilateral pupil abnormality divided into the early and late
groups are needed in the future.
Disclosure statement
The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper.
Funding information
This work was supported by Fund of Science and Technology of
Yixing (2014-14), and Fund of Six Best Talent of Jiangsu (WSN-025).
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