The RESCUEicp decompressive craniectomy study

Lead Research Organisation: University of Cambridge
Department Name: Neurosurgery

Abstract

Trauma is the commonest cause of death in patients under the age of 40 with head injury implicated in at least half the number of cases. Following injury the brain swells within a rigid box (the skull), resulting in increased pressure, reduced oxygenation and cell death. Our research (an international multi-centre randomised study - www.RESCUEicp.com) aims to determine whether patients with severe injury will benefit from an operation (decompressive craniectomy) which involves removing part of the skull bone to relieve pressure. Patients with raised pressure are randomised to receive either the operation or on-going medical treatment. The study has now recruited 126 patients from 22 centres in 8 countries out of a target of 600. The overall aim of the study is to determine whether this type of surgery reduces disability and mortality.

Technical Summary

Head injury is a major cause of morbidity and mortality. The fundamental pathophysiological process is the development of an escalating cycle of brain swelling, increase in intra-cranial pressure (ICP), reduction in blood supply and oxygen delivery, and energy failure. This results in further swelling, enhancing brain injury and poor outcome. The management of head-injured patients is therefore directed at measuring ICP using fine transducers inserted through the skull and treating these adverse processes. In some patients this can be achieved using fundamental medical measures, with ventilation, sedation and drugs including inotropes and mannitol, but in others raised ICP becomes refractory. These patients may benefit from an operation called ‘decompressive craniectomy‘ which involves removing part of the skull and opening the dura lining the brain. There are several studies in the literature investigating the role of decompressive craniectomy in traumatic brain injury. These demonstrate a wide range of outcomes with no clear consensus regarding the indication for the operation. We have therefore commenced the pilot phase of an international multi-centre randomised trial coordinated by University of Cambridge Neurosurgery in collaboration with the European Brain Injury Consortium to investigate whether decompressive craniectomy results in improvement in outcome and surrogate endpoints compared to contemporary optimal medical management.

The trial is recruiting from centres experienced in the intensive care management of head injury. The target study group are ventilated ICP monitored patients with refractory intracranial hypertension. The inclusion criteria are patients with head injury, age 10-65 years with an abnormal CT scan requiring ICP monitoring with raised ICP (25mmHg) refractory to initial medical treatment measures. The exclusion criteria are bilateral fixed and dilated pupils, bleeding diathesis and devastating injury not expected to survive for 2urs.

The two arms are continuation of optimal medical management (including barbiturates) versus surgery (decompressive craniectomy). Outcome is assessed using the Extended Glasgow Outcome Score at six months as the primary measure and SF-36 questionnaire, control of ICP, time in intensive care, time to discharge from the neurosurgical unit as secondary measures. The study aims to recruit 500 patients from approximately 60 centres worldwide.

The results of the study will be used to improve the design of protocols for the treatment of raised ICP following head injury, with the overall goal being to improve outcome. The pilot phase of the study has completed recruiting 50 patients from 12 centres. Further study information is available at www.RESCUEicp.com

Publications

10 25 50
 
Title Video recording 
Description Collaboration with NEJM - RESCUEicp results 
Type Of Art Film/Video/Animation 
Year Produced 2016 
Impact Dissemination of RESCUEicp results. Multiple hits. 
 
Description Citation in Cochrane review
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
Impact Cochrane review on decompressive craniectomy states that the results of RESCUEicp trial are eagerly awaited in order to inform guidelines
 
Description Consensus conference of intracranial pressure monitoring in traumatic brain injury
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact The consensus meeting output is expected to consolidate the place of ICP monitoring in the management of brain-injured patients
URL http://link.springer.com/article/10.1007/s00701-014-2127-4
 
Guideline Title Brain Trauma Foundation Head Injury Guidelines
Description Decompressive Craniectomy
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
Impact Implementation of decompressive craniectomy as part of a randomised study.
 
Description Decompressive craniectomy consensus meeting
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Impact Consensus statement on decompressive craniectomy - a procedure that saves live with a wide distribution of clinical outcomes
 
Description Department of Health Clinical Advisory Group (Trauma)
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact On-going- due to be published 2010.
 
Description Guidelines of Italian Neurosurgical and Neurocritical Care Societies
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
Impact Invitation to contribute to the development of guidelines for managing severe head injury
 
Description Multidisciplinary consensus conference on Multimodality Monitoring in Neurocritical Care
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact Consensus statement is expected to act as a catalyst for improving management of brain-injured patients.
URL http://link.springer.com/article/10.1007/s12028-014-0041-5
 
Description Neurosurgical Representative on the current NICE Committee revising the NICE guidelines for the early management of head injury in adults and children (due to be published published in 2013/4)
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Head injury guidelines
 
Description Training
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Increasing understanding of performing randomised studies in intensive care. Increasing understanding of the use of decompressive craniectomy as part of protocol-driven therapy.
 
Description 2013 EU collaborative grant CENTER-TBI [Prospective longitudinal data collection and Comparative Effectiveness Research (CER) for traumatic brain injury (TBI)] Start 1st October 2013. 78 months Total Euro 29,998,903 University of Cambridge Euro 2,840,158
Amount € 29,000,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 11/2014 
End 10/2019
 
Description 2013 NIHR HTC Grant- Brain Injury. Start 1st January 2013 4 years £800,000 (co-applicant)
Amount £800,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2014 
End 12/2018
 
Description 2014 NIHR HTA Grant 12/201/10 Multi-centre randomised control trial comparing the clinical and cost effectiveness of trans-foraminal epidural steroid injection to surgical microdiscectomy for the treatment of chronic radicular pain secondary to prolapsed
Amount £1 (GBP)
Funding ID HTA/12/201/10 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2015 
End 12/2018
 
Description 2015 NIHR RCF funding for research nurse 1 year £30000
Amount £30,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2015 
End 03/2016
 
Description British Heart Foundation Grant for Subarachnoid Haemorrhage Statin Study
Amount £1,200,000 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2011 
End 01/2014
 
Description Cambridge BRC - Clinical Neurosciences Component (PI Head Injury Research)
Amount £1,260,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2011 
End 12/2015
 
Description Canadian Institute for Health Research Fellowship to fund research fellow Dr CG/Canadian Institute for Health Research
Amount £24,000 (GBP)
Organisation Canadian Institutes of Health Research 
Sector Public
Country Canada
Start 01/2007 
End 01/2008
 
Description Evelyn Trust, Neurorehabilitation Grant/Evelyn Trust
Amount £1,250,000 (GBP)
Organisation The Evelyn Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2009 
End 10/2014
 
Description Evidence based planning solution for TBI
Amount € 4,200,000 (EUR)
Funding ID 270259 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 02/2011 
End 12/2014
 
Description MRC Collaborative Grant for Acute Brain Injury
Amount £1,300,000 (GBP)
Funding ID G0600986 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2007 
End 07/2012
 
Description Medical Research Council Experimental Medicine Grant . Translating experimental stroke therapy to patients: determination of optimal dosing and biological efficacy of IL-1ra.
Amount £603,000 (GBP)
Funding ID G0502030 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2006 
End 07/2009
 
Description NIHR BRC
Amount £1,892,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2017 
 
Description NIHR Brain Injury MedTech Co-operative
Amount £1,250,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2022
 
Description NIHR Global Health
Amount £1,800,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2017 
End 07/2020
 
Description NIHR HTA Grant 12/35/57 RESCUE-ASDH decompressive craniectomy start July 2014 end 2019 £1,655,739 (lead applicant and chief investigator)
Amount £1,655,739 (GBP)
Funding ID NIHR HTA Grant 12/35/57 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2014 
End 08/2021
 
Description NIHR Health Technology Assessment Grant- Risk adjustment in Neurocritical care (RAIN)
Amount £617,000 (GBP)
Funding ID HTA/07/37/29 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 01/2009 
End 01/2012
 
Description Research Fellowship Medical Research Council / Royal College of Surgeons of England to fund research fellow Mr AH
Amount £188,500 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2009 
End 07/2012
 
Description Research Fellowship Royal College of Surgeons of England to fund research fellow Mr AH
Amount £45,000 (GBP)
Organisation Royal College of Surgeons of England 
Sector Learned Society
Country United Kingdom
Start 07/2008 
End 07/2009
 
Description Research Fellowship Royal College of Surgeons of England to fund research fellow Mr AK
Amount £50,000 (GBP)
Organisation Royal College of Surgeons of England 
Sector Learned Society
Country United Kingdom
Start 12/2012 
End 11/2013
 
Description Research Fellowship Royal College of Surgeons of England to fund research fellow Mr MG
Amount £50,000 (GBP)
Organisation Royal College of Surgeons of England 
Sector Learned Society
Country United Kingdom
Start 08/2010 
End 08/2011
 
Description Wellcome Trust Grant for Imaging (Magnetic Resonance Spectroscopy in Head Injury)
Amount £2,800,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2006 
End 01/2011
 
Title Neurosurgical Research Laboratories 
Description Brain tumour, brain imaging and cell culture lab plus neurochemistry lab 
Type Of Material Improvements to research infrastructure 
Year Produced 2016 
Provided To Others? Yes  
Impact Multidisciplinary research output 
 
Title New head injury data collection and follow up proforma. 
Description Multicentre study follow up to 2 years, validation of SF-36 questionnaire following head injury. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact 96% follow up in a multl-centre head injury study. 
 
Title Contribution to TARN 
Description Outcome from traumatic brain injury in the UK. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact Availability of head injury outcome data in the open access literature. 
 
Title Cranioplasty registry 
Description UK Cranioplasty Registry in eet up 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact On-going. Improvement in cranioplasty technique and results. 
 
Title GNOS 
Description Data collection for surgery for head injury 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact On-going 
 
Title Neurotrauma registry 
Description Registry for head injury 
Type Of Material Data handling & control 
Year Produced 2017 
Provided To Others? Yes  
Impact On-going international registry 
 
Description 13C-labelled microdialysis 
Organisation University of Calgary
Department Section of Neurosurgery
Country Canada 
Sector Academic/University 
PI Contribution 13C labelling studies of brain metabolism using microdialysis in traumatic brain injury patients.
Collaborator Contribution Our collaborator has visited us in Cambridge on a Visiting Fellowship (awarded by the Canadian Institute of Health Research). The collaboration is ongoing and our collaborator is a Co-investigator on a current MRC Research Grant (PI: Peter Hutchinson, G1002277 ID 98489).
Impact Publication: Gallagher CN, Carpenter KL, Grice P, Howe DJ, Mason A, Timofeev I, Menon DK, Kirkpatrick PJ, Pickard JD, Sutherland GR, Hutchinson PJ. The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study. Brain. 2009 Oct;132(Pt 10):2839-2849. PubMed PMID: 19700417.
Start Year 2006
 
Description British Neurosurgical Trainee Research Collaborative 
Organisation Society of British Neurological Surgeons
Country United Kingdom 
Sector Learned Society 
PI Contribution AK and PH led the efforts to establish the British Neurosurgical Trainee Research Collaborative. The BNTRC is a research network for trainees which will aim to develop, run and support neurosurgical trials.
Collaborator Contribution The SBNS has very generously supported this initiative since its inception.
Impact PMID: 22583319
Start Year 2012
 
Description British Neurotrauma Group 
Organisation Society of British Neurological Surgeons
Country United Kingdom 
Sector Learned Society 
PI Contribution Initiative to set up a special-interest group within the Society of British Neurological Surgeons
Collaborator Contribution Increasing understanding of the issues surrounding decompressive craniectomy in head injury
Impact The first academic meeting of the group took place in 2010 (October). The meeting was attended by neurosurgeons, neurorehabilitation consultants, endocrinologists, neurologists and specialist nurses.
Start Year 2008
 
Description Engineering - finite element analysis of decompressive craniectomy 
Organisation University of Cambridge
Department Department of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Increasing the understanding of the clinical consequences of brain deformation after craniectomy
Collaborator Contribution Finite element analysis of decompressive craniectomy
Impact Publications
Start Year 2010
 
Description International Multicentre Randomised Trial 
Organisation European Brain Injury Consortium (EBIC)
Country European Union (EU) 
Sector Charity/Non Profit 
PI Contribution Study set-up, patient recruitment and data collection
Collaborator Contribution Patient recruitment
Impact Recruitment of 280 patients from 43 centres in 17 countries
 
Description International Multicentre Randomised Trial 
Organisation International Neurotrauma Society (INTS)
Country Hungary 
Sector Charity/Non Profit 
PI Contribution Study set-up, patient recruitment and data collection
Collaborator Contribution Patient recruitment
Impact Recruitment of 280 patients from 43 centres in 17 countries
 
Description International Multicentre Randomised Trial 
Organisation Society of British Neurological Surgeons
Country United Kingdom 
Sector Learned Society 
PI Contribution Study set-up, patient recruitment and data collection
Collaborator Contribution Patient recruitment
Impact Recruitment of 280 patients from 43 centres in 17 countries
 
Description NIHR Global Neurotrauma Research Group 
Organisation National Institute for Health Research
Department Global Health Research Unit on Global Surgery
PI Contribution We lead this NIHR Group.
Collaborator Contribution Please see website http://neurotrauma.world.
Impact Please see http://neurotrauma.world
Start Year 2017
 
Title Cranial access device 
Description MRI compatible device to transmit monitoring probes into the brain. 
IP Reference GB2330080 
Protection Patent granted
Year Protection Granted
Licensed Yes
Impact Use in clinical practice
 
Title Decompressive Craniectomy 
Description Decompressive craniectomy following traumatic brain injury. 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2006
Development Status Under active development/distribution
Impact International trial. Current stage: late clinical evaluation. Recruitment completed. 
 
Title New Chemistry Sensor 
Description Brain chemistry sensor 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2016
Development Status Under active development/distribution
Impact On-going 
 
Title ICMplus 
Description ICU monitoring software. Developed by Marek Czosnyka and Peter Smielewski. 
Type Of Technology Software 
Impact Take up internationally 
 
Title ORION collaboration 
Description SBNS registries. Led by Alexis Joannides 
Type Of Technology Webtool/Application 
Year Produced 2010 
Impact Development of registries. 
 
Company Name ICMplus - Cambridge Enterprise. Led by Marek Czosnyka and Peter Smielewski. 
Description Medical software, 
Impact Improvement of monitoring and data capture in Intensive Care.
 
Description BBC lifesavers 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact BBC TV program

Multiple discussions with colleagues and public
Year(s) Of Engagement Activity 2013
 
Description British Science Festival, 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk given at the British Science Festival, Newcastle, September 2013.

This activity generated interest in our studies on head-injured patients.
Year(s) Of Engagement Activity 2006,2013
 
Description Cambridge Science Festival Talk on Sports Concussion 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Science Festival Talk
Year(s) Of Engagement Activity 2017
 
Description DIY-SOS 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact National TV program
Year(s) Of Engagement Activity 2018
 
Description Headway 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Discussions with local Headway (head injury charity)

Increased awareness of traumatic brain injury
Year(s) Of Engagement Activity 2006,2007,2008,2009
 
Description Interview and Video for BBC 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Our group has been using computer aided design and 3D printing in medical quality titanium to manufacture cranial plates for human use. I was approached to carry out an interview and filming in the operating theatre and with a patient. This was distributed on BBC digital (http://www.bbc.co.uk/news/av/entertainment-arts-41325582/brain-surgery-revolution), and broadcast three times on the regional BBC network (Look East) reaching an audience of approximately 2.6 million people. I was also interviewed in person on the live evening broadcast.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/news/av/entertainment-arts-41325582/brain-surgery-revolution
 
Description Media RESCUEicp results 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dissemination of the RESCUEicp results published in the BMJ
Year(s) Of Engagement Activity 2016
 
Description National Research Collaborative Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation about trial set-up and management within a trainee research collaborative. This spread awareness about the trial throughout other surgical disciplines and allowed us to share ways to improve trainee involvement in management of a clinical trial.
Year(s) Of Engagement Activity 2015
 
Description Publication of patient's journey after a head injury with patient as the first author 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This paper which described the journey after a head injury from the patient's perspective will allow healthcare professionals to understand the challenges brain-injured patients face.

The paper has been tweeted a few times on Twitter
Year(s) Of Engagement Activity 2014
URL http://europepmc.org/abstract/MED/24737905
 
Description RESCUEicp interviews for radio 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact RESCUEicp study results dissemination
Year(s) Of Engagement Activity 2016,2017
 
Description Royal College of Surgeons Research Evening 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Royal College of Surgeons fundraising event - approximately 50 members of the public

Increasing funding for research
Year(s) Of Engagement Activity 2010
 
Description SBNS presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation of outline of trial and recruitment plan to neurosurgeons, trainees and students throughout the UK attending a national neurosurgical conference. Ability to engage new centres and principal investigators.
Year(s) Of Engagement Activity 2015
 
Description Science Festival Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Cambridge Science Festival
Year(s) Of Engagement Activity 2015,2016,2017