3. Randomised controlled trial comparing the efficacy of decompressive craniectomy versus optimal medical management for the treatment of refractory intracranial hypertension following brain trauma - Collaboration between the University of Cambridge Departments of Neurosurgery/Neurointensive care and the European Brain Injury Consortium (EBIC)
4. Introduction 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. 1,500/100,000 of the population attend A&E departments with a head injury 300/100,000 per year are admitted to hospital 15/100,000 per year are admitted to Neurosurgical Units 9/100,000 per year die from head injury
5. Vicious cycle The fundamental pathophysiological process following head injury is the development and propagation of an escalating cycle of: Brain swelling Increase in intracranial pressure Reduction in blood supply & oxygen delivery Energy failure The cycle continues and ultimately leads to a poor outcome. RESCUEicp aims to determine the effectiveness of an operation to intercept this cycle, treat the brain swelling and improve outcome.
6. Secondary events in TBI Diffuse axonal injury Inflammation BBB disruption Apoptosis Necrosis Brain trauma Oedema formation Ischemia Energy failure Cytokines Calcium Eicosanoids Polyamines ROS Acetylcholine Shohami, 2000 Green – pathophysiological processes; Yellow – various mediators
8. 1783 Alexander Monro: - cranium was a "rigid box" - filled with a "nearly incompressible brain“ - total volume tends to remain constant In 1824 George Kellie confirmed many of Monro's early observations. Monro A. Observations on the structure and function of the nervous system. Edinburgh, Creech & Johnson 1823 p.5 Kellie G. An account of the appearances observed in the dissection of two of the three individuals presumed to have perished in the storm of the 3rd, and whose bodies were discovered in the vicinity of Leith on the morning of the 4th November 1821 with some reflections on the pathology of the brain. Trans Med Chir Sci, Edinburgh 1824;1:84-169
9. History Decompressive craniotomy - first described by T. Annandale in 1894 H. Cushing reports subtemporal and suboccipital decompression to alleviate high ICP in 1905
10. Hypotheses – the principle research questions Decompressive craniectomy results in an improvement in the Extended Glasgow Outcome Score compared to optimal medical treatment 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.
11. The Cochrane Database of Systematic ReviewsThe Cochrane Library. Copyright 2006The Cochrane Collaboration Volume (1) 2006 Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury Sahuquillo J, Arikan F There is no evidence to support the routine use of decompressive craniectomy to reduce unfavourable outcome in adults with severe TBI and refractory high ICP. However, the results of nonrandomised trials and controlled trials with historical controls suggest that decompressive craniectomy may be a useful option when maximal medical treatment has failed to control ICP
12. DATA COLLATION Cochrane Injuries Group’s Trial register CENTRAL MEDLINE EMBASE Best Evidence Clinical Practice Guidelines PubMed CINAHL National Research Register Google Scholar Hand-searched relevant conference proceedings Contacted experts in the field and authors of included studies
13. Should head injured patients with persistently high ICP undergo decompressive craniectomy? ? + ICP >25mmHg ------>
14. Rationale Hence the need for 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 & severe disability and persistent vegetative state have profound social and economic consequences 2. 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.
15. The 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).
16. Ethics Approval Eastern MREC gave approval on the 22nd October 2003 (ref:03/5/059) Start Date -1stJanuary 2004 Target number – 400 patients DECRA – August 2003 to April 2010 Total of 155 patients The study showed a significant decrease in ICP in patients in the surgical group. However, although ICP was lowered by surgery, ICP was not excessively high in the medical group (mean ICP below 24 mmHg pre-randomisation).
17. RESCUEicp differs from DECRA ICP threshold (25 vs. 20mmHg) Duration of refractory raised ICP (>1 hour vs. 15 minutes) Timing of surgery - any time after injury vs. within 72 hours post-injury) Acceptance of contusions Longer follow up (2 years).
18. Countries of Recruitment United Kingdom United States Canada China Czech Republic Germany Greece Italy Latvia Malaysia Russia Saudi Arabia Singapore Spain Turkey
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20. With abnormal CT scan requiring ICP monitoring (Brain Trauma Foundation Guidelines)
23. Patients who have immunological, hepatic or renal compromise can be included, but type and extent of their impairment must be included.
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25. 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
26. The Protocol The major objective of this protocol is to maintain ICP<25 mmHg by applying treatment measures in a number of stages. - Stage I to V (modifications made to a two staged protocol)
27. Stage I - Propofol, Fentanyl,& Atracurium - 10 – 15 degrees head up - paCO2 4.5 – 5.0KPa Stage IV - Temp 33 – 34C Stage V - Thiopentone - Decompressive craniectomy Stage II - External Ventricular Drainage (EVD) Stage III - Inotropes - paCO2 4.0KPa - Temp 35C
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29. Surgery The surgical treatment will comprise: (a) for unilateral hemisphere swelling / a large unilateral fronto-temporo-parietal craniectomy or (b) for bilateral diffuse hemisphere swelling a large bilateral fronto-temporo-parietal craniectomy
30. Recommended technique To accommodate variation in surgical practice and preferences between international neurosurgical centres the protocol was designed with the following essential requirements: Wide (at least 12cm in diameter) decompressive craniectomy Opening the dura and leaving it open (with an option of duroplasty) Avoiding tight bandaging or positioning patient head on the craniotomy side, after decompression Documenting the size of the created bony window in the data collection proforma
31. Outcome measurement Primary measure 6 month extended Glasgow Outcome Score - Blind assessment using a postal questionnaire Secondary measures 2 year extended Glasgow Outcome Score 6 month and 2 year SF-36 quality of life assessment SF-60 – health economic analysis ICP control Time in neuro-intensive care Time to discharge from neurosurgical unit
33. UPDATEAs at September 201014th International Conference on Intracranial Pressure and Brain MonitoringTubingen, Germany. Over 265 patients had been recruited so far (299 as at March 2011) Patients were from more than 40 centres in 17 countries The follow up rate at 6 months is 96% Evaluation of the first 120 patients showed equal distribution of characteristics between the two arms Overall, 80% of the patients were male 5% were hypoxic and 13% hypotensive at initial presentation 73% were initially GCS 3-8, 16% GCS 9-12 and 12% 13 -15
35. References 1. American College of Surgeons Committee on Trauma. Advanced Trauma Life Support for Doctors. Chicago: American College of Surgeons, 1997. 2. Report of the working party on the management of patients with head injuries. London: Royal College of Surgeons of England, 1999. 3. Jennett B, MacMillan R. Epidemiology of head injury. Br Med Journal 1981;282:101-4 4. Hutchinson PJ, Kirkpatrick PJ, Addison J, Jackson S, and Pickard JD. The management of minor traumatic brain injury. J AccidEmerg Med 15, 84-88. 1998. 5. Patel HC, Menon DK, Tebbs S, Hawker R, Hutchinson PJ, Kirkpatrick PJ. Specialist neurocritical care and outcome from head injury. Intensive Care Med 2002;28:547-53. 6. Menon DK. Cerebral protection in severe brain injury: physiological determinants of outcome and their optimisation. Br Med Bull 1999;55:226-58. 7. Menon DK, Matta BF. Intensive care after acute head injury. In: Matta B, Menon D, Turner J, eds. Neuroanesthesia and Neurointensive Care. London: Greenwich Medical Media 2000: 301-17.
36. 8. Gaab MR, Rittierodt M, Lorenz M, Heissler HE. Traumatic brain swelling and operative decompression: A prospective investigation. Acta NeurochirSuppl Wien 1990;51:326-8. 9. Hatashita S, Koga N, Hosaka Y, Tagaki S. Acute subdural hematoma: Severity of injury, surgical intervention, and mortality. Neurol Med Chir(Tokyo) 1993;33:13-8. 10. Polin RS, Shaffery ME, Bogaev CA, Tisdale N, Germanson T, Bocchichio B , Jane JA. Decompressive bifrontal craniectomy in the treatment of severe refractory posttraumatic cerebral oedema. Neurosurgery 1997;41:84-94. 11. Kunze E, Meixensberger J, Janka M, Sorensen N, Roosen K. Decompressive craniectomy in patients with uncontrollable intracranial hypertension. Acta NeurochirSuppl 1998;71:16-8. 12. Kleist-Welch Guerra W, Gaab MR, Dietz H, Mueller JU, Piek J, Fritsch MJ. Surgical decompression for traumatic brain swelling: Indications and results. J Neurosurg 1999;90:187-96. 13. Munch E, Horn P, Schurer L, Piepgas A, Torsten P, Schmidek P. Management of severe traumatic brain injury by decompressive craniectomy. Neurosurgery 2000;47:315-23. etc.
