Acta Neurochir (2006) [Suppl] 96: 1720

6 Springer-Verlag 2006
Printed in Austria

Decompressive craniectomy in traumatic brain injury: the randomized multicenter

RESCUEicp study (www.RESCUEicp.com)
P. J. Hutchinson1,2, E. Corteen1,2, M. Czosnyka1,2, A. D. Mendelow2, D. K. Menon1,2, P. Mitchell2,
G. Murray2, J. D. Pickard1,2, E. Rickels2, J. Sahuquillo2, F. Servadei2, G. M. Teasdale2, I. Timofeev2,
A. Unterberg2, and P. J. Kirkpatrick1,2
1 University of Cambridge, Addenbrookes Hospital, Cambridge, UK
2 European Brain Injury Consortium, Cambridge, UK

Summary
The RESCUEicp (Randomized Evaluation of Surgery with
Craniectomy for Uncontrollable Elevation of intracranial pressure)
study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic
brain injury and raised intracranial pressure that does not respond
to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study.
Keywords: Head injury; traumatic brain injury; intracranial pressure; decompressive craniectomy.

Introduction
Severe head injury is a major cause of morbidity and
mortality worldwide [1, 10]. Of the pathophysiological
processes implicated in traumatic brain injury, one of
the most fundamental is an escalating cycle of brain
swelling, increase in intracranial pressure (ICP), reduction in blood and oxygen supply, energy failure, and
cell death. The goal for management of these patients
is, therefore, to prevent secondary insults, reduce
swelling and ICP, and maintain blood supply, oxygen
delivery, and the energy status of the brain. This management goal applies at the trauma scene, during
transportation, in the emergency department, in the
operating room, and in the intensive care unit.
In order to assist in the management of patients with
traumatic brain injury on the intensive care unit, protocols have been developed providing a step-wise
approach to the control of brain swelling and raised

ICP [2, 7, 8]. Targets have been established for ICP

(<2025 mmHg) and cerebral perfusion pressure
(CPP) (CPP mean arterial pressure
ICP [>60
70 mmHg]). These protocols commence with relatively simple therapeutic maneuvers including sedation, ventilation, and head-up position for nursing. If
these basic measures fail to control brain swelling,
more advanced medical treatment can be applied including the application of inotropes, hypertonic saline,
mannitol, and hypothermia. External ventricular
drainage of cerebrospinal uid may also be feasible,
depending on the size of the lateral ventricles. While
brain swelling and ICP can be controlled in most
patients with these basic measures, in others ICP is
refractory and more advanced therapy needs to be
considered. Options for these patients include the
implementation of barbiturate coma and/or a decompressive surgical procedure such as decompressive craniectomy. Evidence of benet for both of these therapies is currently sparse [4, 9].
Decompressive craniectomy is not a new operation.
The phenomenon of brain decompression has been
in existence for hundreds of years, commencing
with trephination by the ancient Greeks, followed by
Kocher approximately 100 years ago. Most recently,
the operation has been performed in the context of
modern, sophisticated neuro-intensive care.
In terms of controlling raised ICP, decompressive
craniectomy is performed in several neurosurgical
units world-wide, but there is no consensus on if and

P. J. Hutchinson et al.

18

when to proceed with the surgery. There are several

concerns regarding the application of decompressive
craniectomy. These include failure to control ICP despite decompression, and herniation of brain through
the craniectomy defect. In addition, the operation
may be being performed unnecessarily in patients destined for a good prognosis, and pertinent to patients
with poor prognosis, may save life at the expense of
creating vegetative state and severe disability.
In terms of the current literature on the application
of decompressive craniectomy to patients with traumatic brain injury, there have been several studies published (for review, see [3]). These are predominantly
observational studies and demonstrate a wide range
of outcomes (good recovery 29%69%; mortality
11%40%). There has been one attempt at randomization in the pediatric age group, which showed a
signicant dierence in outcome, favoring patients
randomized to surgery [11]. This study had a number
of limitations, which were recognized by the authors,
including sample size, outcome evaluation, and prolonged study duration.
In view of the widely diering results in these published studies, consensus on the role of decompressive
craniectomy has not been achieved. This has resulted
in proposals for randomized controlled trials. Three
such trials have been proposed: an American trial,
an Australasian trial (International Multicenter
Randomized Controlled Trial on Early Decompressive Craniectomy DECRA), and a European study
(Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial
pressure RESCUEicp).
This manuscript outlines the protocol for the RESCUEicp study a randomized control trial comparing
the ecacy of decompressive craniectomy versus optimal medical management for the treatment of refractory intracranial hypertension following brain trauma.
This is a multi-center trial organized as a collaboration
between the University of Cambridge Departments
of Neurosurgery/Neuro-intensive Care and the European Brain Injury Consortium.
Methodology
The RESCUEicp study is a randomized trial comparing optimal medical management with surgery
(decompressive craniectomy) for the management of
intracranial hypertension following head injury, refractory to rst-line treatment. The trial aims to recruit

patients from centers experienced in the intensive care

management of head injury. The target study group includes ventilated, ICP-monitored patients with refractory intracranial hypertension. Post-randomization,
the trial comprises 2 arms: continuation of optimal
medical management versus surgery (decompressive
craniectomy).
Hypotheses
The principal hypothesis for the RESCUEicp study
is that the application of decompressive craniectomy
to head-injured patients with raised ICP refractory to
medical treatment results in improved outcome. Specically, 1) that decompressive craniectomy results in
an improvement in the Extended Glasgow Outcome
Score compared to optimal medical treatment and, 2)
that decompressive craniectomy results in an improvement in surrogate endpoint measures (including specic outcome measures [SF-36 questionnaire], control
of ICP, time in intensive care, and time to discharge
from the neurosurgical unit) compared to optimal
medical treatment.
Protocol
Patient inclusion and exclusion criteria for the trial
are shown in Table 1. Approval for the study has been
obtained from the UK National Ethics Committee,
with ethical approval in other countries on-going. To
avoid delays in treatment, it is recommended that consent for participation in the study is obtained from next
on kin at time of patient admission to the neurosurgical unit, with randomization performed following failure to control ICP with initial treatment. Patients are
managed on intensive care units using the trial protocol (Fig. 1). The major objective of this protocol is
to maintain ICP < 25 mmHg by applying treatment
measures in 3 stages.

Table 1. Inclusion and exclusion criteria for the RESCUEicp study

Inclusion criteria

Exclusion criteria

Head injury requiring ICP monitoring

bilateral xed and dilated

pupils
bleeding diathesis
follow up not possible
devastating injury not
expected to survive 24
hours

Age 1065 years

Abnormal CT scan
Patients may have had an immediate
operation for a mass lesion but not
a decompressive craniectomy

Decompressive craniectomy in traumatic brain injury

19

Fig. 1. Summary of RESCUEicp decompressive craniectomy protocol. The protocol is divided into 3 stages. Stage 1 comprises initial treatment measures. If the ICP > 25 mmHg after the implementation of Stage 1, the patient enters Stage 2 comprising a number of further options
to control ICP. If the ICP is >25 mmHg after the implementation of Stage 2, the patient enters Stage 3 and is randomized to on-going medical
treatment or decompressive craniectomy

Stage 1: initial treatment measures

Patients are sedated, relieved of pain, and ventilated
(with the option for paralysis), in the head-up position
for nursing and invasive monitoring (ICP, central
venous pressure, and arterial lines as a minimum).
ICP is assessed at this stage. If the ICP < 25 mmHg,
the above medical treatment continues. If the ICP >
25 mmHg, Stage 2 is implemented (with the option of
a repeat scan to investigate the possibility of an evolving mass lesion).

taining SjvO2 > 55%), hypertonic saline, moderate

cooling (3436  C) but not severe hypothermia, loop
diuretics, and steroids. Barbiturates are not implemented as part of Stage 2, but are reserved as part of
continued medical treatment following randomization. This clause enables a direct comparison between
the ecacy of decompressive craniectomy and extended medical treatment including the introduction
of barbiturate coma.
Stage 3: randomization

Stage 2: advanced treatment measures

In Stage 2, the following measures can be considered, all of which are optional: an external ventricular
drain (depending on the size of the lateral ventricles),
mannitol, inotropes (to increase the mean arterial pressure to maintain a CPP of >60 mmHg), arterial carbon dioxide 3.5 kPa to 4.5 kPa (can be monitored
with jugular venous oxygen saturation sensors main-

If ICP remains > 25 mmHg for 112 hours despite

Stage 1 and 2 measures, then the patient is randomized
to either continued Stage 2 medical treatment including barbiturates (e.g. thiopentone boluses infusion
48 mg/kg/hr), or to surgical treatment (decompressive craniectomy). Treatment following randomization should be implemented within 46 hours.
The surgical treatment comprises 2 options: (a)

20

P. J. Hutchinson et al.: Decompressive craniectomy in traumatic brain injury

for unilateral hemisphere swelling, a large unilateral

fronto-temporo-parietal craniectomy or, (b) for bilateral diuse hemisphere swelling, a large bilateral
fronto-temporo-parietal craniectomy from the frontal
sinus anteriorly to the coronal suture posteriorly and
pterion laterally with a wide dural opening (pedicles
based on the superior sagittal sinus medially) with the
option of division of the falx anteriorly.
If the patient is randomized to continued medical
treatment, no decompressive surgery is performed at
the time of randomization, but may be performed later
at the clinicians discretion if the patient subsequently
deteriorates (for example, prolonged and unacceptably
high ICP > 40 mmHg with compromised CPP). This
clause is required if a situation arises whereby the
treating physician feels that withholding surgery is acting against the best interest of the individual patient;
the interests of the patient always prevails over those
of science and society [6]. The same principle applies
to barbiturates in the decompressive craniectomy
group.
Outcome is assessed at discharge using the Glasgow
Coma Score, and at 6 months using the Extended
Glasgow Outcome Score [12]. Secondary endpoints
are assessment of outcome using the SF-36 quality of
life questionnaire [5], assessment of ICP control, time
in intensive care, and time to discharge from the neurosurgical unit. For patients undergoing decompressive
craniectomy, it is recommended that the bone ap is
replaced within 6 months of the initial injury.
Recruitment of patients commences with a pilot
phase comprising 50 patients. Overall the study aims
to recruit 400 patients (200 in each arm of the study)
for a 15% dierence in outcome (dierence in favorable outcome from 45%60%) (power 80%, p
0.05). The pilot phase of the RESCUEicp study has
now commenced, with 19 of out the pilot study target
of 50 patients recruited.
Conclusion
Despite considerable interest in the concept of decompressive craniectomy for patients with traumatic
brain injury, including several peer-reviewed publications, current opinion on the role of this operation
is divided. Randomized studies are now indicated to
obtain good quality Class I evidence. The RESCUEicp study has now commenced and aims to establish
whether decompressive craniectomy results in improvement in outcome compared to contemporary op-

timal medical management. Contact with the RESCUEicp group in Cambridge, UK, can be made via the
website www.RESCUEicp.com or by e-mail pjah2@
cam.ac.uk.

Acknowledgments
This RESCUEicp protocol has evolved as a result of discussions
between representatives of the University of Cambridge and the European Brain Injury Consortium. P. J. Hutchinson is supported by
an Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship. We wish to acknowledge the members of
the data monitoring committee, Mr. M. D. M. Shaw, Dr. H. K.
Richards, Dr. M. Smith, Prof. Lennart Persson.

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Correspondence: P. J. Hutchinson, Academic Department of
Neurosurgery, University of Cambridge, Box 167, Addenbrookes
Hospital, Cambridge, UK, CB2 2QQ. e-mail: pjah2@cam.ac.uk