EARLYDRAIN- outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

Jürgen Bardutzky, Jens Witsch, Eric Jüttler, Stefan Schwab, Peter Vajkoczy, Stefan Wolf, Jürgen Bardutzky, Jens Witsch, Eric Jüttler, Stefan Schwab, Peter Vajkoczy, Stefan Wolf

Abstract

Background: Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet.

Methods/design: This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge.

Discussion: Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.

Trial registration: ClinicalTrials.gov NCT01258257.

Figures

Figure 1
Figure 1
EARLYDRAIN study algorithm. The EARLYDRAIN study algorithm showing the course of events after the initial aneurysmal subarachnoid hemorrhage (SAH) and the subsequent surgical or interventional aneurysm treatment. The study includes two groups, a treatment group receiving lumbar CSF-drainage (LD) and a control group receiving no lumbar drainage according to protocol (NoLD). The timing of the patient's consent to study participation, randomization, cranial imaging and assessment of clinical outcome is indicated by the shaded boxes. Imaging on day 7 to 10 is scheduled according to local guidelines. If a local center performs no routine cerebrovascular imaging for vasospasm screening in patients without clinical suspicion, it may be omitted.

References

    1. van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain. 2001;124:249–78. doi: 10.1093/brain/124.2.249.
    1. Stehbens WE. Aneurysms and Anatomical Variation of Cerebral Arteries. Arch Pathol. 1963;75:45–64.
    1. Keyrouz SG, Diringer MN. Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11:220. doi: 10.1186/cc5958.
    1. Crowley RW, Medel R, Dumont AS. et al.Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage. Stroke. 2011;42:919–23. doi: 10.1161/STROKEAHA.110.597005.
    1. Pluta RM, Hansen-Schwartz J, Dreier J. et al.Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31:151–8. doi: 10.1179/174313209X393564.
    1. Diringer MN, Bleck TP, Claude Hemphill J, Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care. 2011.
    1. Allen GS, Ahn HS, Preziosi TJ. et al.Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983;308:619–24. doi: 10.1056/NEJM198303173081103.
    1. Otten ML, Mocco J, Connolly ES Jr, Solomon RA. A review of medical treatments of cerebral vasospasm. Neurol Res. 2008;30:444–9. doi: 10.1179/174313208X284089.
    1. Komotar RJ, Hahn DK, Kim GH. et al.Efficacy of lamina terminalis fenestration in reducing shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage: a systematic review. Clinical article J Neurosurg. 2009;111:147–54.
    1. Kasuya H, Shimizu T, Kagawa M. The effect of continuous drainage of cerebrospinal fluid in patients with subarachnoid hemorrhage: a retrospective analysis of 108 patients. Neurosurgery. 1991;28:56–9. doi: 10.1227/00006123-199101000-00009.
    1. Widenka DC, Wolf S, Schurer L, Plev DV, Lumenta CB. Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurol Neurochir Pol. 2000;34:56–60.
    1. Klimo P, Kestle JR, MacDonald JD, Schmidt RH. Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg. 2004;100:215–24. doi: 10.3171/jns.2004.100.2.0215.
    1. Kwon OY, Kim YJ, Cho CS, Lee SK, Cho MK. The Utility and Benefits of External Lumbar CSF Drainage after Endovascular Coiling on Aneurysmal Subarachnoid Hemorrhage. J Korean Neurosurg Soc. 2008;43:281–7. doi: 10.3340/jkns.2008.43.6.281.
    1. Tuettenberg J, Czabanka M, Horn P. et al.Clinical evaluation of the safety and efficacy of lumbar cerebrospinal fluid drainage for the treatment of refractory increased intracranial pressure. J Neurosurg. 2009;110:1200–8. doi: 10.3171/2008.10.JNS08293.
    1. Staykov D, Speck V, Volbers B. et al.Early recognition of lumbar overdrainage by lumbo-ventricular pressure gradient. Neurosurgery. 2011;68(5):1187–91.
    1. Molyneux AJ, Kerr RS, Yu LM. et al.International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366:809–17. doi: 10.1016/S0140-6736(05)67214-5.
    1. Kreiter KT, Mayer SA, Howard G. et al.Sample size estimates for clinical trials of vasospasm in subarachnoid hemorrhage. Stroke. 2009;40:2362–7. doi: 10.1161/STROKEAHA.109.547331.
    1. Rankin J. Cerebral vascular accidents in patients over the age of 60. II Prognosis Scott Med J. 1957;2:200–15.
    1. Lindley RI, Waddell F, Livingstone M, Warlow CP, Dennis MS, Sandercock PAG. Can simple questions assess outcome after stroke? Cerebrovasc Dis. 1994;4:314–32. doi: 10.1159/000108501.
    1. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968;28:14–20. doi: 10.3171/jns.1968.28.1.0014.
    1. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980;6:1–9. doi: 10.1227/00006123-198001000-00001.
    1. Scheithauer S, Burgel U, Ryang YM. et al.Prospective surveillance of drain associated meningitis/ventriculitis in a neurosurgery and neurological intensive care unit. J Neurol Neurosurg Psychiatry. 2009;80:1381–5. doi: 10.1136/jnnp.2008.165357.

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