The RESCUEicp study is an international prospective multi-centre randomised control trial comparing the efficacy of decompressive craniectomy versus optimal medical management for the treatment of refractory intracranial hypertension following brain trauma.
 
The trial is organised as a collaboration between the University of Cambridge Departments of Neurosurgery / Neuro-intensive Care and the European Brain Injury Consortium.
 

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Introduction
Hypotheses

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Rationale for a study
The proposed trial
Inclusion criteria
Exclusion criteria
Approval, consent and randomisation
The protocol
Power
Outcome measures
Acknowledgements
References
 
 
 
 
Introduction - the problem to be addressed
 
Head injury is a major cause of morbidity and mortality worldwide. Trauma is the leading cause of death in the first four decades of life with head injury being implicated in at least half the number of cases.1 In the UK , 1500 per 100 000 of the population (total one million) attend Accident and Emergency Departments with a head injury 2, 300 per 100 000 per year are admitted to hospital, 15 per 100 000 per year are admitted to Neurosurgical Units and 9 per 100 000 per year die from head injury.3;4
 
Recent advances in the management of head injury have occurred at several levels including prevention, pre-hospital care, immediate hospital care (trauma teams, advanced trauma life support courses), acute hospital care (neuro-intensive care units with protocol driven therapy) and post-acute hospital care (rehabilitation). Recently, recommendations have been produced by the Royal College of Surgeons, including the transfer of all patients with severe head injury to regional neurosurgical units.2 Despite improvement in outcome during the 1990s as shown in the data from the UK East Anglian Regional Audit of Head Injury 5 (table 1), mortality and morbidity remain high and controversy continues both about the fundamental concepts of treatment and about specific techniques. 
 
The fundamental pathophysiological process following head injury is the development and propagation of an escalating cycle of brain swelling, increase in intra-cranial pressure (ICP), reduction in blood supply and oxygen delivery, energy failure and further swelling, enhancing brain injury and poor outcome (figure 1). The aim of this trial is to determine the effectiveness of an operation (decompressive craniectomy) to intercept this cycle, treat brain swelling and improve outcome.
 
 
 
Hypotheses - the principle research questions to be answered
 
The application of decompressive craniectomy to head-injured patients with raised intra-cranial pressure (ICP) refractory to medical treatment results in improvement in outcome:
 
(1) Decompressive craniectomy results in an improvement in the Extended Glasgow Outcome Score compared to optimal medical treatment
 
(2) Decompressive craniectomy results in an improvement in surrogate endpoint measures (including specific 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.
 
 
 
Rationale for a study - why is a trial needed now?
 
Cerebral ischaemia secondary to injury and brain swelling within the tight confines of the skull precipitates a cascade of adverse metabolic events which culminate in a cycle of further swelling, reductions in blood flow and in oxygen and glucose supply. Therapy to reduce ICP following acute brain injury is the cornerstone to the management of these patients. The introduction of protocol driven therapy with a number of stages to reduce ICP has been one of the factors leading to potential improvements in outcome.6;7
Two surgical manoeuvres can be employed to reduce ICP:

(1) The application of external ventricular drains to drain cerebro-spinal fluid.
 
(2) Decompressive craniectomy (removal of a large area of skull with opening of the dura to increase the volume of the cranial cavity, facilitating a reduction in ICP; figure 2 ).
 
Several reports in the literature investigate the role of decompressive craniectomy in traumatic brain injury 8-20. These studies demonstrated a wide range of clinical outcome, with no clear consensus regarding the indication for the operation.  The generally accepted way to resolve the role of any therapy for neurotrauma is to obtain class I evidence by performing prospective randomised trials. We are therefore proposing a multi-centre European trial, co-ordinated by the University of Cambridge Department of Neurosurgery, in collaboration with the European Brain Injury Consortium (EBIC). Such a trial should be performed for the following reasons:

1. Severe head injury is common and severe disability and persistent vegetative state has profound social and economic consequences
 
2. The current data (small studies, class II and III evidence, poor follow up) are inconclusive
 
3. A randomised study has the potential to address the concerns that the operation does not influence the favourable outcome of good prognosis patients and that it shifts outcome from death to vegetative state / severe disability in poor prognosis patients.
 
4. To establish the incidence of complications resulting from this procedure e.g. post-operative haematoma, infection.
 
 
 
The proposed trial
 
The study will be a randomised trial comparing optimal medical management with surgery (decompressive craniectomy) for the management of intra-cranial hypertension following head injury, refractory to first-line treatment.
 
The trial will recruit from centres experienced in the intensive care management of head injury. The target study group will be ventilated ICP-monitored patients with refractory intracranial hypertension. The two arms will be the continuation of optimal medical management versus surgery (decompressive craniectomy).
 
The study has evolved as a result of discussions between potential study centres with the aim of providing flexibility in terms of the intensive care management of the patients yet sufficient protocol discipline to enable the hypotheses to be addressed.  
 
 
 
Inclusion criteria
 

 
 
 
Exclusion criteria
   
 
Approval, consent and randomisation
 
Approval for the study will be obtained from the relevant local and national ethics committees. Consent for the study will be obtained from next on kin on admission to the neurosurgical unit with randomisation performed after stage 2 to avoid delays in treatment.
 
The principle of randomising neurosurgical patients to medical treatment versus craniotomy has already been proven with the successful implementation of the STICH trial (Surgical Trial of IntraCerebral Haemorrhage).21
 
             
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Randomised Evaluation of Surgery with Craniectomy for
Uncontrollable Elevation of Intra-Cranial Pressure