REVIEW URRENT C OPINION
Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Stefan Wolf
Purpose of review The amount of blood in the basal cisterns is predictive for the final outcome after aneurysmal subarachnoid hemorrhage (SAH) and clinical problems such as delayed cerebral ischemia and angiographic vasospasm. A lumbar drainage presents an additional, physiologically appealing treatment. In contrast to an external ventricular drain, stasis of clots is thought to be prevented and clearance of the basal cisterns accelerated. In theory, patients with higher clinical grades and dense layers of subarachnoid blood should benefit most. Recent findings A positive signal but so far no conclusive evidence for lumbar drains in SAH is available from retrospective data. Two large series exist, one after clipping and one after endovascular coiling of the aneurysm leading to the index hemorrhage. The only high-quality large prospective trial failed to prove a better neurologic outcome at 6 months, but investigated predominantly good grade patients with less severe hemorrhage. Further data from another phase III trial is still pending. A concern on the safety of lumbar drains is not supported. Summary At present, no definite conclusions and recommendations on lumbar drains in patients after aneurysmal SAH are warranted. Keywords aneurysmal subarachnoid hemorrhage, blood clot clearance, lumbar drainage, neurocritical care
INTRODUCTION Patients after aneurysmal subarachnoid hemorrhage (SAH) had been shown to have a mortality up to 25% in contemporary observational series [1], and up to 10% in randomized trials [2–4]. Up to 30% of survivors suffer from severe permanent disability and every other patient experiences depression and reduced quality of life during the first year of recovery [5]. Predictive for the final outcome, as well as medical complications during the acute phase such as delayed cerebral ischemia and angiographic vasospasm, is the amount of blood in the basal cisterns. In 1980, Fisher et al. [6] proposed the still most widely used graduation scale to estimate risks from the initial computed tomography (CT) scan. Patients with a clot thickness of more than 1 mm showed a chance of more than 95% for developing symptomatic vasospasm, whereas patients with smaller clots or a diffuse subarachnoid layer of blood experienced a low-to-moderate risk. The scale was based on a rather small patient number, and CT technology did improve considerably since. The www.co-criticalcare.com
findings from Fisher et al. [6] were reconfirmed in several larger patient series using contemporary CT scanners with increased resolution [7,8], thus validating the amount of blood in the basal cisterns as an independent predictor for delayed cerebral ischemia, angiographic vasospasm, and final outcome. Therefore, it is appealing to address removal of the subarachnoid blood after aneurysm rupture as a treatment objective.
PHYSIOLOGICAL RATIONALE A principal means of clearing the basal cisterns is by irrigation under sight. This option is feasible in patients requiring open surgery, but not in patients Department of Neurosurgery, Charite University Medicine, Berlin, Germany Correspondence to Stefan Wolf, Department of Neurosurgery, Charite University Medicine, Campus Virchow, Augustenburger Platz 1, Berlin 13353, Germany. E-mail: [email protected] Curr Opin Crit Care 2015, 21:120–126 DOI:10.1097/MCC.0000000000000183 Volume 21 Number 2 April 2015
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Wolf
RETROSPECTIVE DATA
KEY POINTS It is well known that after aneurysmal SAH, fluid from the spinal canal is way more ‘bloody’ than cerebrospinal fluid derived by an external ventricular drain. Drainage of cerebrospinal fluid via a lumbar drain may present a valuable treatment option to remove blood from the basal cisterns. Retrospective work is largely in favor for the lumbar drainage approach after aneurysmal SAH, but presents important shortcomings. So far, prospective data are not supportive on the use of lumbar drains, with data from one large phase III trial still pending. No definite conclusions can be given at present, and subgroups such as the more severely affected patients may be the only ones gaining benefit from a lumbar drain.
in whom endovascular coiling of the aneurysm is the chosen treatment option. However, opening the lamina terminalis during surgery and irrigating the basal cisterns neither led unequivocally to a better neurologic outcome nor at least reduced the rate of posthemorrhagic hydrocephalus after aneurysmal SAH [9,10]. Given the current trend to endovascular aneurysm treatment after two randomized trials [2,11], it is unlikely that new data will readdress the question of blood removal via open irrigation. Drainage of cerebrospinal fluid (CSF) via an external ventricular device (EVD) is used to relieve acute posthemorrhagic hydrocephalus. Concerning the blood within the basal cisterns, however, it seems to promote stasis of clots, instead of clearance. The incidence of shunt dependence is reported to be higher after excess drainage through the ventricular route [12,13]. The rationale might be that CSF is more lightweight than blood, and the latter stays in the basal cisterns because of gravity. This is visually evident in patients after aneurysmal SAH who are treated with both an EVD and a lumbar drain [14 ]. Although CSF from an external ventricular drain may appear clean, the blood in the lumbar compartment is often diagnostic for SAH without further laboratory testing. Clearance of subarachnoid blood is more rapid with a lumbar drain than an external ventricular drain [15], and the rate of necessary permanent CSF diversion with a ventriculoperitoneal shunt appears lower than predicted by historical data [16]. Therefore, removal of blood with a lumbar drain may propose an eligible treatment option after SAH. &&
Although the intraoperative use of lumbar drains is well known to neurosurgeons to relieve the basal cisterns and facilitate aneurysm clipping, the effect on a patient’s outcome was studied only in the last decade.
Patients after clipping &&
Klimo et al. [14 ] report on their experience with lumbar drains after SAH in a series of 167 out of 266 patients treated within a 10-year time frame in Salt Lake City; 81 patients did receive a lumbar drain and 86 did not. All patients were allotted to one of two dedicated teams of neurovascular surgeons by day of admission. The only difference in treatment between both teams was that one of them favored the use of lumbar drains whereas the other did not. EVDs were used to treat hydrocephalus as clinically required. Only patients with dense subarachnoid blood clots, defined as Fisher 3 (thick blood level in the basal cisterns), Fisher 4 (blood clot in the ventricles or the parenchyma, but no blood in the basal cisterns), or Fisher 3 þ 4 (a compound definition unique to this article, indicating dense subarachnoid blood and intraventricular or intraparenchymal hemorrhage) were considered as candidates for a lumbar drain. Patients in poor neurological condition without significant improvement after resuscitation as well as patients with Fisher grades 1 and 2 were not included. All patients except three in each group treated with coiling got surgical aneurysm obliteration within 36 h of admission. Questions asked by the researchers and defined as primary outcome parameters were whether the use of a lumbar drain decreased clinical evident vasospasm and the need for endovascular intervention, reduced vasospasminduced infarction, and whether the patients had differences in the disposition at discharge and final outcome as assessed by Glasgow Outcome Scale (GOS) at 1–3 months post-discharge. Patients in the group treated with lumbar drains experienced less vasospasm (17 vs. 51%) and were less often treated with endovascular interventions (17 vs. 45%). Vasospastic infarctions were seen less often in the lumbar drainage group (7 vs. 27%). Patients in the treatment group were more often discharged home (54 vs. 25%) and had more often a favorable GOS score of 5 at 1–3 months (71 vs. 35%). All results were highly significant in the univariate analysis. The differences in angiographic vasospasm, endovascular intervention, and vasospastic infarctions additionally proved to be significantly better for the lumbar drainage group in a multivariate logistic regression, too, corrected for age, Fisher grade, Hunt–Hess grade, intraoperative
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rupture, need for external ventricular drain on admission, and aneurysm location. Deceased patients in both the groups accounted for 3 and 5%, respectively. Multivariate data was not presented on disposition at discharge and GOS outcome. Despite a preselection of patients to those with at least dense subarachnoid blood layers and therefore with a predominantly clinical high severity grade of hemorrhage, the mortality in both the groups was rather low, compared with other contemporary work. This raises questions about the external validity of the study, and it is difficult to use its results for sample size calculation of a prospective trial. Nevertheless, the study by Klimo et al. [14 ] led to a paradigm change in many neurosurgical departments all over the world, and lumbar drains got increasingly used for therapy of patients with SAH. &&
Patients after coiling
The various subgroup analyses remain underpowered. Correcting for three different potential confounders in subgroups of four patients is simply meaningless. Given the way of analysis, imbalances of patient numbers and severity grades in both arms and the mortality differences, internal as well as external validity of this study need to be questioned.
Further retrospective data At least one contemporary case series presented at a medical conference does exist [18]. Another work addresses the safety and tries to establish criteria for a lumbar drain after aneurysmal SAH [19]. Although these articles are supportive for a lumbar drain, Kasuya et al. [12] found that removal of large amounts of CSF could be detrimental. A variety of external ventricular, cisternal and lumbar drains were used in this work, and it is impossible to extract the evidence for a particular way of CSF diversion.
&
In 2008, a study by Kwon et al. [17 ] from Cheonan, South Korea, addressed the use of lumbar drains in patients with SAH and endovascular aneurysm treatment. In the light of coiling being increasingly used for aneurysm obliteration worldwide, this question was imminent. In contrast to surgical clipping, during coiling there is no exposure to a patient’s basal cisterns and clearance of the blood by other means may become even more important. Forty-seven patients with and 60 patients without a lumbar drain were investigated. The abstract states the study as being randomized; however, the main text is silent on this. Therefore, given the imbalance in group sizes, it is assumed that the data is a convenience series rather than a prospective trial, thus diminishing largely its quality of evidence. Patients with all clinical grades and Fisher grades 2–4 were included, the higher grades being overrepresented in the conventional treatment group. The original Fisher scale was enhanced with separate grades for patients with intraventricular hemorrhage. Results were strikingly different in mortality, with 2% deceased patients in the lumbar drainage group and 15% in the conventional treatment group. Vasospasm (23 vs. 63%) and long-term outcome of survivors (GOS 5 at 1–6 months 72 vs. 37% in the conventional group) were in favor of a lumbar drainage as well. Results were additionally analyzed with logistic regression corrected for baseline imbalances as well as subgroups according to the different Fisher classifications and the benefit of lumbar drains proved significant there, too. Of note is the effect of a lumbar drain being decreased in patients with intraventricular hemorrhage, counterintuitive to logical reasoning. 122
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PROSPECTIVE EVIDENCE The authors of the study on lumbar drains in patients after clipping [14 ] and the accompanying editorial acknowledged the need for further prospective data, with such a study being underway. This trial was mentioned in a technical discussion a few years after the initial publication as well [19]. Unfortunately, the study was abandoned because of lack of resources (Paul Klimo, Jr, personal communication). &&
The LUMAS trial The first prospective data available was a singlecenter trial from Leeds, UK, presented by Al-Tamimi et al. [20 ]. The lumbar drainage in aneurysmal SAH (LUMAS) trial investigated the use of a lumbar drain in patients with World Federations of Neurological Surgeons clinical grades 1–3, thus excluding a more severely affected population. Two hundred ten patients were randomized equally to either conventional treatment or additional application of a lumbar drain, giving 105 patients per group. Primary outcome parameter was the prevalence of a delayed ischemic neurologic deficit during the acute phase of treatment, and secondary outcome included assessment of the neurologic condition by the modified Rankin scale [21]. The main finding was that lumbar drainage reduced the prevalence of delayed ischemic neurologic deficit and improved early clinical outcome. However, there was no difference at 6 months between both the groups in their neurologic condition, as measured with the modified Rankin scale. A positive trend for less delayed &&
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Wolf
ischemic neurologic deficits, with statistical significance only being present in Fisher grade 3 patients, was found in a secondary analysis of patients treated per protocol, in contrast to the primary intention-totreat analysis. No differences in infarctions depicted by magnetic resonance imaging in patients with delayed ischemic neurologic deficit or in the requirement for permanent CSF diversion with a ventriculoperitoneal shunt were noted. Five patients in the conventional group and four patients in the lumbar drainage group were deceased at 6 months. The patient population investigated in the LUMAS trial was in stark contrast to the retrospective work, reported by Klimo et al. [14 ]. The latter focused on clinical and radiological high-grade patients, whereas these were excluded per protocol in the prospective trial. Therefore, LUMAS was at least underpowered to detect differences in outcome between the groups. The main assets of this prospective trial were strict diagnostic criteria for the delayed ischemic neurologic deficit as well as a wealth of neuroradiologic imaging without missing data. LUMAS appears carefully performed and has not received concerns of creditability or external validity. &&
Further completed prospective work Ha¨nggi et al. [22] investigated prospectively irrigation with urokinase lysis via two intrathecal lumbar catheters, followed by intrathecal nimodipine lavage and kinetic head rotation in comatose patients. Controls were randomized to standard treatment. The multimodal treatment concept was applied in 20 patients, without definite results. The study was halted prematurely after paraparesis that occurred in two patients in the treatment group [22]. The combined application of several treatment regimens renders it impossible to judge the impact of single measures on outcome. In 2014, Sun et al. [23] reported on a randomized trial on external ventricular drains vs. lumbar drains in 148 patients of World Federation of Neurological Societies grade III who were treated with coil embolization. The main finding was no outcome differences between the groups, measured by the GOS at 2 months. Nevertheless, the authors suggested lumbar drain placement to be better than external ventricular drain placement, without explicit scientific reasoning. The EVD group showed a higher rate of intracranial hemorrhage after drainage insertion, which is difficult to assess, as no information on potential anticoagulation of the patients after coiling was presented. Vasospasm was diagnosed by transcranial doppler and similar in both the groups, as well as infarctions diagnosed by CT. Infection rates and the rate of required ventriculoperitoneal
shunting for hydrocephalus were equal in both the groups. The report was silent on the criteria for drain placement, with hydrocephalus as one potential indication being excluded per protocol. No data on intracranial pressure (ICP) after drainage placement were given. Moreover, data on the amount of CSF drainage and catheter removal criteria were lacking. Beyond confirming the safety of a lumbar drain after aneurysmal SAH, it is difficult to extract further scientific knowledge from this study because of missing details in the publication. Another prospective trial, so far published only in abstract form, compared 30 patients with lumbar drainage to 30 controls with standard treatment [24]. Borkar [24] found a statistically significant reduction of clinical vasospasm as well as significantly less vasospasm-related infarctions. In addition, a better GOS value at 1 and 3 months in the lumbar drainage group was reported, without quoting significance levels. From the data presented, it is impossible to rate the evidence added by this trial.
Work in progress: EARLYDRAIN A further prospective randomized phase III trial on lumbar drains is currently undertaken. EARLYDRAIN is a multicenter, multinational study and recruits patients after aneurysmal SAH of all clinical grades [25]. Patients are randomized to receive a lumbar drain after securing the aneurysm or to best conventional therapy. The study is designed as pragmatic trial to ensure that every center treats patients to the best of its expertise, with no restrictions on additional medical therapy or endovascular rescue procedures applied in case of angiographic vasospasm. The primary outcome parameter is neurological status evaluated by the modified Rankin score at 6 months. At the time of writing, slightly more than two thirds of the anticipated 300 patients are enrolled. Given the current recruitment rate and the required 6-month follow-up, results are awaited for 2016. In the study protocol, no restrictions on clinical grades or hemorrhage severity are specified. When planning the study, the results of the LUMAS study were still pending. Furthermore, the EARLYDRAIN investigators recognized two different attitudes in potential collaborators. Most centers expressed concerns on the safety of a lumbar drain, especially in high-grade patients. Others, however, had already included the use of a lumbar drain in their clinical practice, mostly referring to the study of Klimo et al. [14 ]. This presented a clinical equipoise not warranting restrictive inclusion criteria on clinical or radiological grades. Regardless of the final result of EARLYDRAIN being positive or negative, its data will &&
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fuel the discussion, which patients will benefit most from a lumbar drain.
SAFETY Both large retrospective series as well as the prospective LUMAS trial reported no increased rate of general complications for lumbar drains in SAH [14 ,17 ,20 ]. The rate for device-induced meningitis was estimated at 2% [20 ]. Similar findings were presented in the prospective randomized comparison study on ventricular vs. lumbar drains [23]. The feared risk of a lumbar drain in patients with acute brain injury is downward herniation of the cerebellar tonsils in the foramen magnum. None of the completed trials, nor the interim safety analysis of EARLYDRAIN, are indicative of an increased mortality rate. In the general literature, surprisingly, few publications on this complication are available, even if underreporting is considered [19,26 ,27]. In contrast, the documented number of patients treated for various reasons with a lumbar drain, even in case of raised ICP, is increasing steadily, without a relevant rate of devastating complications [27–30]. Knol et al. [31] investigated the width of the third and fourth ventricle as well as their ratio to &&
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determine whether lumbar drainage may be feasible without causing harm. However, no specific relation could be given. Judging the CT scans and eyeballing the size of the basal cisterns may be inconclusive (Fig. 1). Kawahara et al. [32] pointed out that CSF hypovolemia with consecutive brain sagging may happen at normal-to-low ICP levels, with its sequelae usually being benign. In a given patient, additional physiologic reasoning by observation of the ventriculolumbar pressure gradient may be helpful. Drainage will be possible in case of a communicating cerebrospinal fluid pathway, whereas caution is warranted in case of a blocked CSF circulation. In open CSF pathways, the ICP is delivered via fluid column to the spinal canal [33]. The pressure measured via a stopcock mounted on the lumbar drain will equal the pressure from an external ventricular drain, both zeroed on the same level at the external auditory channel (Fig. 2). Staykov et al. [26 ] present a seminal case where blockage of the circulation occurs at a normal ICP level and an increasing pressure gradient develops over hours. They recommend stopping lumbar drainage in case of a cerebrolumbar pressure difference of more than 5 mmHg, and this was forwarded and recommended in the EARLYDRAIN protocol as &
FIGURE 1. Basal cisterns on computed tomography. Images in the (a)–(d) upper row are from a patient with aneurysmal subarachnoid hemorrhage where fluid diversion was performed at 5 ml/h without problems. The (e)–(h) lower row is from a patient where the pressures of the cerebrolumbar gradient reached values above the recommended safety difference of 5 mmHg. Lumbar drainage was required to be ceased in this patient. Both series of images are from the current EARLYDRAIN study. The differences in basal cisterns are subtle and may not be detected by imaging alone. 124
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Wolf 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 30 ICP_PAR 28 ICP_EVD 26 24 ICP_LD 22 20 18 16 14 12 10 8 6 4 2 0 ABP
[mmHg]
[mmHg]
CPP
4/9 17:30
4/9 18:00
4/9 18:30
4/9 19:00
4/9 19:30
4/9 20:00
4/9 20:30
4/9 21:00
FIGURE 2. Data from a patient with subarachnoid hemorrhage of the EARLYDRAIN study, recorded with a multimonitoring system (ICMplus, Cambridge, UK). Intracranial pressure (ICP) is measured via a parenchymal probe (ICP_par), an external ventricular device (ICP_EVD), and a lumbar drain (ICP_LD). Zeroing of fluid-coupled ICP_EVD and ICP_LD was applied to the external auditory channel. The lumbar drain is opened intermittently, but in between catches the same ICP level as the other devices. No apparent gradient between ICP measurement devices. Cerebral perfusion pressure (CPP) is measured as difference between mean arterial blood pressure (ABP) and ICP_par.
additional safety procedure. Of course, clinicians need to be aware that there never will be prospective level 1 evidence that this additional pressure monitoring on the lumbar drain guarantees safety, beyond its physiologic rationale being sound. If performed, it requires expertise and caution and it prohibits a permanent CSF diversion at a certain height. Rather, it is required to open the drain on demand and close it during the rest of the time to ensure adequate monitoring (Fig. 2). In the EARLYDRAIN protocol, stopping lumbar CSF diversion in case of ICP levels higher than 20 mmHg is the recommended action, regardless of the cerebrospinal gradient.
OPEN QUESTIONS The results of the EARLYDRAIN study need to be awaited before more definite recommendations may be given. If warranted at all, it is plausible that application of lumbar drains should be restricted for high-grade patients and spared in patients with less risk for delayed cerebral ischemia. One advantage of lumbar drains in SAH may be decreasing the incidence of posthemorrhagic hydrocephalus. Available evidence from the retrospective case series as well as the prospective LUMAS study is inconclusive. Both retrospective cohort series specified 5–10 ml/h of drainage via the lumbar route but remained silent on the actual amount of CSF drained. LUMAS reported an average drainage rate of 138 ml/24 h and a median duration of 5 days. For
safety reasons and to homogenize treatment, the EARLYDRAIN protocol restricts drainage via the lumbar route to 5 ml/h and requires, if necessary, additional drainage via an external ventricular drain for the first 8 days after hemorrhage. Investigation of different drainage regimens, as well as possible administration of fibrinolytics, will be worthwhile [34,35].
CONCLUSION A lumbar drainage presents an additional, physiologically appealing treatment concept for patients after aneurysmal SAH. However, so far, no conclusive evidence is available from retrospective data and the only large high-quality prospective trial failed to prove a better neurologic outcome at 6 months. Concerns about the safety of lumbar drains are not backed up by existing literature, but neither is early adoption in existing treatment algorithms. Therefore, at present, no definite conclusion and recommendation on lumbar drains in patients with SAH is warranted. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest The author is the Senior Investigator of the EARLYDRAIN trial.
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REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Prabhakaran S, Fonarow GC, Smith EE, et al. Hospital case volume is associated with mortality in patients hospitalized with subarachnoid hemorrhage. Neurosurgery 2014; 75:500–508. 2. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002; 360:1267–1274. 3. Macdonald RL, Higashida RT, Keller E, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke J Cereb Circ 2012; 43:1463–1469. 4. Macdonald RL, Higashida RT, Keller E, et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol 2011; 10:618–625. 5. Kreiter KT, Rosengart AJ, Claassen J, et al. Depressed mood and quality of life after subarachnoid hemorrhage. J Neurol Sci 2013; 335:64–71. 6. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980; 6:1–9. 7. Claassen J, Bernardini GL, Kreiter K, et al. Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke J Cereb Circ 2001; 32:2012–2020. 8. Wilson DA, Nakaji P, Abla AA, et al. A simple and quantitative method to predict symptomatic vasospasm after subarachnoid hemorrhage based on computed tomography: beyond the Fisher scale. Neurosurgery 2012; 71:869–875. 9. Komotar RJ, Zacharia BE, Otten ML, et al. Controversies in the endovascular management of cerebral vasospasm after intracranial aneurysm rupture and future directions for therapeutic approaches. Neurosurgery 2008; 62:897– 905. 10. 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; 111:147–154. 11. McDougall CG, Spetzler RF, Zabramski JM, et al. The barrow ruptured aneurysm trial. J Neurosurg 2012; 116:135–144. 12. 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; 28:56–59. 13. Widenka DC, Wolf S, Schu¨rer L, et al. Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurol Neurochir Pol 2000; 34: 56–60. 14. Klimo P, Kestle JRW, MacDonald JD, et al. Marked reduction of cerebral && vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 2004; 100:215–224. A retrospective study that illustrates the concept of lumbar drains in aneurysmal SAH and shows convincing data concerning improvement of outcome. 15. Maeda Y, Shirao S, Yoneda H, et al. Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg 2013; 115:965–970. 16. Ormond DR, Dressler A, Kim S, et al. Lumbar drains may reduce the need for permanent CSF diversion in spontaneous subarachnoid haemorrhage. Br J Neurosurg 2013; 27:171–174.
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17. Kwon OY, Kim Y-J, Kim YJ, et al. The utility and benefits of external lumbar CSF drainage after endovascular coiling on aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc 2008; 43:281–287. The second most important retrospective study, dealing with patients after coiling. 18. Tizi K, Gu¨resir E, Beck J, et al. The effect of lumbar drainage on cerebral vasospasm and infarction after subarachnoid haemorrhage (abstract). 60th Annual Meeting of the German Society of Neurosurgery (DGNC) 2009; Mu¨nster, Germany. 19. Hoekema D, Schmidt RH, Ross I. Lumbar drainage for subarachnoid hemorrhage: technical considerations and safety analysis. Neurocrit Care 2007; 7:3–9. 20. Al-Tamimi YZ, Bhargava D, Feltbower RG, et al. Lumbar drainage of cerebrosp&& inal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS). Stroke J Cereb Circ 2012; 43:677–682. The only high-quality prospective trial on lumbar drains. This is at present the best evidence available. First results in a less severely affected patient population are negative, though. 21. Rankin J. Cerebrovascular accidents in patients over the age of 60: prognosis. Scott Med J 1957; 2:200–215. 22. Ha¨nggi D, Eicker S, Beseoglu K, et al. A multimodal concept in patients after severe aneurysmal subarachnoid hemorrhage: results of a controlled single centre prospective randomized multimodal phase I/II trial on cerebral vasospasm. Cent Eur Neurosurg 2009; 70:61–67. 23. Sun C, Du H, Yin L, et al. Choice for the removal of bloody cerebrospinal fluid in postcoiling aneurysmal subarachnoid hemorrhage: external ventricular drainage or lumbar drainage? Turk Neurosurg 2014; 24:737–744. 24. Borkar SA. 183 spinal cerebrospinal fluid drainage for prevention of vasospasm in aneurysmal subarachnoid haemorrhage: a prospective randomized controlled study. Neurosurgery 2013; 60:180–181. 25. Bardutzky J, Witsch J, Ju¨ttler E, et al. EARLYDRAIN – outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial. Trials 2011; 12:203. 26. Staykov D, Speck V, Volbers B, et al. Early recognition of lumbar overdrainage & by lumboventricular pressure gradient. Neurosurgery 2011; 68:1187–1191. This article illustrates the concept of cerebrolumbar pressure gradients, which may present an important tool for safe lumbar drainage in patients with high-grade SAH. 27. Wang K, Liu Z, Chen X, et al. Clinical characteristics and outcomes of patients with cerebral herniation during continuous lumbar drainage. Turk Neurosurg 2013; 23:653–657. 28. 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; 110:1200–1208. 29. Abulhasan YB, Al-Jehani H, Valiquette M-A, et al. Lumbar drainage for the treatment of severe bacterial meningitis. Neurocrit Care 2013; 19:199–205. 30. Murad A, Ghostine S, Colohan AR. A case for further investigating the use of controlled lumbar cerebrospinal fluid drainage for the control of intracranial pressure. World Neurosurg 2012; 77:160–165. 31. Knol DS, van Gijn J, Kruitwagen CLJJ, et al. Size of third and fourth ventricle in obstructive and communicating acute hydrocephalus after aneurysmal subarachnoid hemorrhage. J Neurol 2011; 258:44–49. 32. Kawahara I, Tsutsumi K, Matsunaga Y, et al. Early awareness of cerebrospinal fluid hypovolemia after craniotomy for microsurgical aneurysmal clipping. Acta Neurochir (Wien) 2013; 155:1543–1548. 33. Speck V, Staykov D, Huttner HB, et al. Lumbar catheter for monitoring of intracranial pressure in patients with posthemorrhagic communicating hydrocephalus. Neurocrit Care 2011; 14:208–215. 34. Ramakrishna R, Sekhar LN, Ramanathan D, et al. Intraventricular tissue plasminogen activator for the prevention of vasospasm and hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 2010; 67:110–117. 35. Gerner ST, Kuramatsu JB, Abel H, et al. Intraventricular fibrinolysis has no effects on shunt dependency and functional outcome in endovascular-treated aneurysmal SAH. Neurocrit Care 2014; 21:435–443. &
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Stefan Wolf
Purpose of review The amount of blood in the basal cisterns is predictive for the final outcome after aneurysmal subarachnoid hemorrhage (SAH) and clinical problems such as delayed cerebral ischemia and angiographic vasospasm. A lumbar drainage presents an additional, physiologically appealing treatment. In contrast to an external ventricular drain, stasis of clots is thought to be prevented and clearance of the basal cisterns accelerated. In theory, patients with higher clinical grades and dense layers of subarachnoid blood should benefit most. Recent findings A positive signal but so far no conclusive evidence for lumbar drains in SAH is available from retrospective data. Two large series exist, one after clipping and one after endovascular coiling of the aneurysm leading to the index hemorrhage. The only high-quality large prospective trial failed to prove a better neurologic outcome at 6 months, but investigated predominantly good grade patients with less severe hemorrhage. Further data from another phase III trial is still pending. A concern on the safety of lumbar drains is not supported. Summary At present, no definite conclusions and recommendations on lumbar drains in patients after aneurysmal SAH are warranted. Keywords aneurysmal subarachnoid hemorrhage, blood clot clearance, lumbar drainage, neurocritical care
INTRODUCTION Patients after aneurysmal subarachnoid hemorrhage (SAH) had been shown to have a mortality up to 25% in contemporary observational series [1], and up to 10% in randomized trials [2–4]. Up to 30% of survivors suffer from severe permanent disability and every other patient experiences depression and reduced quality of life during the first year of recovery [5]. Predictive for the final outcome, as well as medical complications during the acute phase such as delayed cerebral ischemia and angiographic vasospasm, is the amount of blood in the basal cisterns. In 1980, Fisher et al. [6] proposed the still most widely used graduation scale to estimate risks from the initial computed tomography (CT) scan. Patients with a clot thickness of more than 1 mm showed a chance of more than 95% for developing symptomatic vasospasm, whereas patients with smaller clots or a diffuse subarachnoid layer of blood experienced a low-to-moderate risk. The scale was based on a rather small patient number, and CT technology did improve considerably since. The www.co-criticalcare.com
findings from Fisher et al. [6] were reconfirmed in several larger patient series using contemporary CT scanners with increased resolution [7,8], thus validating the amount of blood in the basal cisterns as an independent predictor for delayed cerebral ischemia, angiographic vasospasm, and final outcome. Therefore, it is appealing to address removal of the subarachnoid blood after aneurysm rupture as a treatment objective.
PHYSIOLOGICAL RATIONALE A principal means of clearing the basal cisterns is by irrigation under sight. This option is feasible in patients requiring open surgery, but not in patients Department of Neurosurgery, Charite University Medicine, Berlin, Germany Correspondence to Stefan Wolf, Department of Neurosurgery, Charite University Medicine, Campus Virchow, Augustenburger Platz 1, Berlin 13353, Germany. E-mail: [email protected] Curr Opin Crit Care 2015, 21:120–126 DOI:10.1097/MCC.0000000000000183 Volume 21 Number 2 April 2015
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Wolf
RETROSPECTIVE DATA
KEY POINTS It is well known that after aneurysmal SAH, fluid from the spinal canal is way more ‘bloody’ than cerebrospinal fluid derived by an external ventricular drain. Drainage of cerebrospinal fluid via a lumbar drain may present a valuable treatment option to remove blood from the basal cisterns. Retrospective work is largely in favor for the lumbar drainage approach after aneurysmal SAH, but presents important shortcomings. So far, prospective data are not supportive on the use of lumbar drains, with data from one large phase III trial still pending. No definite conclusions can be given at present, and subgroups such as the more severely affected patients may be the only ones gaining benefit from a lumbar drain.
in whom endovascular coiling of the aneurysm is the chosen treatment option. However, opening the lamina terminalis during surgery and irrigating the basal cisterns neither led unequivocally to a better neurologic outcome nor at least reduced the rate of posthemorrhagic hydrocephalus after aneurysmal SAH [9,10]. Given the current trend to endovascular aneurysm treatment after two randomized trials [2,11], it is unlikely that new data will readdress the question of blood removal via open irrigation. Drainage of cerebrospinal fluid (CSF) via an external ventricular device (EVD) is used to relieve acute posthemorrhagic hydrocephalus. Concerning the blood within the basal cisterns, however, it seems to promote stasis of clots, instead of clearance. The incidence of shunt dependence is reported to be higher after excess drainage through the ventricular route [12,13]. The rationale might be that CSF is more lightweight than blood, and the latter stays in the basal cisterns because of gravity. This is visually evident in patients after aneurysmal SAH who are treated with both an EVD and a lumbar drain [14 ]. Although CSF from an external ventricular drain may appear clean, the blood in the lumbar compartment is often diagnostic for SAH without further laboratory testing. Clearance of subarachnoid blood is more rapid with a lumbar drain than an external ventricular drain [15], and the rate of necessary permanent CSF diversion with a ventriculoperitoneal shunt appears lower than predicted by historical data [16]. Therefore, removal of blood with a lumbar drain may propose an eligible treatment option after SAH. &&
Although the intraoperative use of lumbar drains is well known to neurosurgeons to relieve the basal cisterns and facilitate aneurysm clipping, the effect on a patient’s outcome was studied only in the last decade.
Patients after clipping &&
Klimo et al. [14 ] report on their experience with lumbar drains after SAH in a series of 167 out of 266 patients treated within a 10-year time frame in Salt Lake City; 81 patients did receive a lumbar drain and 86 did not. All patients were allotted to one of two dedicated teams of neurovascular surgeons by day of admission. The only difference in treatment between both teams was that one of them favored the use of lumbar drains whereas the other did not. EVDs were used to treat hydrocephalus as clinically required. Only patients with dense subarachnoid blood clots, defined as Fisher 3 (thick blood level in the basal cisterns), Fisher 4 (blood clot in the ventricles or the parenchyma, but no blood in the basal cisterns), or Fisher 3 þ 4 (a compound definition unique to this article, indicating dense subarachnoid blood and intraventricular or intraparenchymal hemorrhage) were considered as candidates for a lumbar drain. Patients in poor neurological condition without significant improvement after resuscitation as well as patients with Fisher grades 1 and 2 were not included. All patients except three in each group treated with coiling got surgical aneurysm obliteration within 36 h of admission. Questions asked by the researchers and defined as primary outcome parameters were whether the use of a lumbar drain decreased clinical evident vasospasm and the need for endovascular intervention, reduced vasospasminduced infarction, and whether the patients had differences in the disposition at discharge and final outcome as assessed by Glasgow Outcome Scale (GOS) at 1–3 months post-discharge. Patients in the group treated with lumbar drains experienced less vasospasm (17 vs. 51%) and were less often treated with endovascular interventions (17 vs. 45%). Vasospastic infarctions were seen less often in the lumbar drainage group (7 vs. 27%). Patients in the treatment group were more often discharged home (54 vs. 25%) and had more often a favorable GOS score of 5 at 1–3 months (71 vs. 35%). All results were highly significant in the univariate analysis. The differences in angiographic vasospasm, endovascular intervention, and vasospastic infarctions additionally proved to be significantly better for the lumbar drainage group in a multivariate logistic regression, too, corrected for age, Fisher grade, Hunt–Hess grade, intraoperative
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rupture, need for external ventricular drain on admission, and aneurysm location. Deceased patients in both the groups accounted for 3 and 5%, respectively. Multivariate data was not presented on disposition at discharge and GOS outcome. Despite a preselection of patients to those with at least dense subarachnoid blood layers and therefore with a predominantly clinical high severity grade of hemorrhage, the mortality in both the groups was rather low, compared with other contemporary work. This raises questions about the external validity of the study, and it is difficult to use its results for sample size calculation of a prospective trial. Nevertheless, the study by Klimo et al. [14 ] led to a paradigm change in many neurosurgical departments all over the world, and lumbar drains got increasingly used for therapy of patients with SAH. &&
Patients after coiling
The various subgroup analyses remain underpowered. Correcting for three different potential confounders in subgroups of four patients is simply meaningless. Given the way of analysis, imbalances of patient numbers and severity grades in both arms and the mortality differences, internal as well as external validity of this study need to be questioned.
Further retrospective data At least one contemporary case series presented at a medical conference does exist [18]. Another work addresses the safety and tries to establish criteria for a lumbar drain after aneurysmal SAH [19]. Although these articles are supportive for a lumbar drain, Kasuya et al. [12] found that removal of large amounts of CSF could be detrimental. A variety of external ventricular, cisternal and lumbar drains were used in this work, and it is impossible to extract the evidence for a particular way of CSF diversion.
&
In 2008, a study by Kwon et al. [17 ] from Cheonan, South Korea, addressed the use of lumbar drains in patients with SAH and endovascular aneurysm treatment. In the light of coiling being increasingly used for aneurysm obliteration worldwide, this question was imminent. In contrast to surgical clipping, during coiling there is no exposure to a patient’s basal cisterns and clearance of the blood by other means may become even more important. Forty-seven patients with and 60 patients without a lumbar drain were investigated. The abstract states the study as being randomized; however, the main text is silent on this. Therefore, given the imbalance in group sizes, it is assumed that the data is a convenience series rather than a prospective trial, thus diminishing largely its quality of evidence. Patients with all clinical grades and Fisher grades 2–4 were included, the higher grades being overrepresented in the conventional treatment group. The original Fisher scale was enhanced with separate grades for patients with intraventricular hemorrhage. Results were strikingly different in mortality, with 2% deceased patients in the lumbar drainage group and 15% in the conventional treatment group. Vasospasm (23 vs. 63%) and long-term outcome of survivors (GOS 5 at 1–6 months 72 vs. 37% in the conventional group) were in favor of a lumbar drainage as well. Results were additionally analyzed with logistic regression corrected for baseline imbalances as well as subgroups according to the different Fisher classifications and the benefit of lumbar drains proved significant there, too. Of note is the effect of a lumbar drain being decreased in patients with intraventricular hemorrhage, counterintuitive to logical reasoning. 122
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PROSPECTIVE EVIDENCE The authors of the study on lumbar drains in patients after clipping [14 ] and the accompanying editorial acknowledged the need for further prospective data, with such a study being underway. This trial was mentioned in a technical discussion a few years after the initial publication as well [19]. Unfortunately, the study was abandoned because of lack of resources (Paul Klimo, Jr, personal communication). &&
The LUMAS trial The first prospective data available was a singlecenter trial from Leeds, UK, presented by Al-Tamimi et al. [20 ]. The lumbar drainage in aneurysmal SAH (LUMAS) trial investigated the use of a lumbar drain in patients with World Federations of Neurological Surgeons clinical grades 1–3, thus excluding a more severely affected population. Two hundred ten patients were randomized equally to either conventional treatment or additional application of a lumbar drain, giving 105 patients per group. Primary outcome parameter was the prevalence of a delayed ischemic neurologic deficit during the acute phase of treatment, and secondary outcome included assessment of the neurologic condition by the modified Rankin scale [21]. The main finding was that lumbar drainage reduced the prevalence of delayed ischemic neurologic deficit and improved early clinical outcome. However, there was no difference at 6 months between both the groups in their neurologic condition, as measured with the modified Rankin scale. A positive trend for less delayed &&
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Wolf
ischemic neurologic deficits, with statistical significance only being present in Fisher grade 3 patients, was found in a secondary analysis of patients treated per protocol, in contrast to the primary intention-totreat analysis. No differences in infarctions depicted by magnetic resonance imaging in patients with delayed ischemic neurologic deficit or in the requirement for permanent CSF diversion with a ventriculoperitoneal shunt were noted. Five patients in the conventional group and four patients in the lumbar drainage group were deceased at 6 months. The patient population investigated in the LUMAS trial was in stark contrast to the retrospective work, reported by Klimo et al. [14 ]. The latter focused on clinical and radiological high-grade patients, whereas these were excluded per protocol in the prospective trial. Therefore, LUMAS was at least underpowered to detect differences in outcome between the groups. The main assets of this prospective trial were strict diagnostic criteria for the delayed ischemic neurologic deficit as well as a wealth of neuroradiologic imaging without missing data. LUMAS appears carefully performed and has not received concerns of creditability or external validity. &&
Further completed prospective work Ha¨nggi et al. [22] investigated prospectively irrigation with urokinase lysis via two intrathecal lumbar catheters, followed by intrathecal nimodipine lavage and kinetic head rotation in comatose patients. Controls were randomized to standard treatment. The multimodal treatment concept was applied in 20 patients, without definite results. The study was halted prematurely after paraparesis that occurred in two patients in the treatment group [22]. The combined application of several treatment regimens renders it impossible to judge the impact of single measures on outcome. In 2014, Sun et al. [23] reported on a randomized trial on external ventricular drains vs. lumbar drains in 148 patients of World Federation of Neurological Societies grade III who were treated with coil embolization. The main finding was no outcome differences between the groups, measured by the GOS at 2 months. Nevertheless, the authors suggested lumbar drain placement to be better than external ventricular drain placement, without explicit scientific reasoning. The EVD group showed a higher rate of intracranial hemorrhage after drainage insertion, which is difficult to assess, as no information on potential anticoagulation of the patients after coiling was presented. Vasospasm was diagnosed by transcranial doppler and similar in both the groups, as well as infarctions diagnosed by CT. Infection rates and the rate of required ventriculoperitoneal
shunting for hydrocephalus were equal in both the groups. The report was silent on the criteria for drain placement, with hydrocephalus as one potential indication being excluded per protocol. No data on intracranial pressure (ICP) after drainage placement were given. Moreover, data on the amount of CSF drainage and catheter removal criteria were lacking. Beyond confirming the safety of a lumbar drain after aneurysmal SAH, it is difficult to extract further scientific knowledge from this study because of missing details in the publication. Another prospective trial, so far published only in abstract form, compared 30 patients with lumbar drainage to 30 controls with standard treatment [24]. Borkar [24] found a statistically significant reduction of clinical vasospasm as well as significantly less vasospasm-related infarctions. In addition, a better GOS value at 1 and 3 months in the lumbar drainage group was reported, without quoting significance levels. From the data presented, it is impossible to rate the evidence added by this trial.
Work in progress: EARLYDRAIN A further prospective randomized phase III trial on lumbar drains is currently undertaken. EARLYDRAIN is a multicenter, multinational study and recruits patients after aneurysmal SAH of all clinical grades [25]. Patients are randomized to receive a lumbar drain after securing the aneurysm or to best conventional therapy. The study is designed as pragmatic trial to ensure that every center treats patients to the best of its expertise, with no restrictions on additional medical therapy or endovascular rescue procedures applied in case of angiographic vasospasm. The primary outcome parameter is neurological status evaluated by the modified Rankin score at 6 months. At the time of writing, slightly more than two thirds of the anticipated 300 patients are enrolled. Given the current recruitment rate and the required 6-month follow-up, results are awaited for 2016. In the study protocol, no restrictions on clinical grades or hemorrhage severity are specified. When planning the study, the results of the LUMAS study were still pending. Furthermore, the EARLYDRAIN investigators recognized two different attitudes in potential collaborators. Most centers expressed concerns on the safety of a lumbar drain, especially in high-grade patients. Others, however, had already included the use of a lumbar drain in their clinical practice, mostly referring to the study of Klimo et al. [14 ]. This presented a clinical equipoise not warranting restrictive inclusion criteria on clinical or radiological grades. Regardless of the final result of EARLYDRAIN being positive or negative, its data will &&
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fuel the discussion, which patients will benefit most from a lumbar drain.
SAFETY Both large retrospective series as well as the prospective LUMAS trial reported no increased rate of general complications for lumbar drains in SAH [14 ,17 ,20 ]. The rate for device-induced meningitis was estimated at 2% [20 ]. Similar findings were presented in the prospective randomized comparison study on ventricular vs. lumbar drains [23]. The feared risk of a lumbar drain in patients with acute brain injury is downward herniation of the cerebellar tonsils in the foramen magnum. None of the completed trials, nor the interim safety analysis of EARLYDRAIN, are indicative of an increased mortality rate. In the general literature, surprisingly, few publications on this complication are available, even if underreporting is considered [19,26 ,27]. In contrast, the documented number of patients treated for various reasons with a lumbar drain, even in case of raised ICP, is increasing steadily, without a relevant rate of devastating complications [27–30]. Knol et al. [31] investigated the width of the third and fourth ventricle as well as their ratio to &&
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determine whether lumbar drainage may be feasible without causing harm. However, no specific relation could be given. Judging the CT scans and eyeballing the size of the basal cisterns may be inconclusive (Fig. 1). Kawahara et al. [32] pointed out that CSF hypovolemia with consecutive brain sagging may happen at normal-to-low ICP levels, with its sequelae usually being benign. In a given patient, additional physiologic reasoning by observation of the ventriculolumbar pressure gradient may be helpful. Drainage will be possible in case of a communicating cerebrospinal fluid pathway, whereas caution is warranted in case of a blocked CSF circulation. In open CSF pathways, the ICP is delivered via fluid column to the spinal canal [33]. The pressure measured via a stopcock mounted on the lumbar drain will equal the pressure from an external ventricular drain, both zeroed on the same level at the external auditory channel (Fig. 2). Staykov et al. [26 ] present a seminal case where blockage of the circulation occurs at a normal ICP level and an increasing pressure gradient develops over hours. They recommend stopping lumbar drainage in case of a cerebrolumbar pressure difference of more than 5 mmHg, and this was forwarded and recommended in the EARLYDRAIN protocol as &
FIGURE 1. Basal cisterns on computed tomography. Images in the (a)–(d) upper row are from a patient with aneurysmal subarachnoid hemorrhage where fluid diversion was performed at 5 ml/h without problems. The (e)–(h) lower row is from a patient where the pressures of the cerebrolumbar gradient reached values above the recommended safety difference of 5 mmHg. Lumbar drainage was required to be ceased in this patient. Both series of images are from the current EARLYDRAIN study. The differences in basal cisterns are subtle and may not be detected by imaging alone. 124
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Rationale for lumbar drains in aneurysmal subarachnoid hemorrhage Wolf 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 30 ICP_PAR 28 ICP_EVD 26 24 ICP_LD 22 20 18 16 14 12 10 8 6 4 2 0 ABP
[mmHg]
[mmHg]
CPP
4/9 17:30
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FIGURE 2. Data from a patient with subarachnoid hemorrhage of the EARLYDRAIN study, recorded with a multimonitoring system (ICMplus, Cambridge, UK). Intracranial pressure (ICP) is measured via a parenchymal probe (ICP_par), an external ventricular device (ICP_EVD), and a lumbar drain (ICP_LD). Zeroing of fluid-coupled ICP_EVD and ICP_LD was applied to the external auditory channel. The lumbar drain is opened intermittently, but in between catches the same ICP level as the other devices. No apparent gradient between ICP measurement devices. Cerebral perfusion pressure (CPP) is measured as difference between mean arterial blood pressure (ABP) and ICP_par.
additional safety procedure. Of course, clinicians need to be aware that there never will be prospective level 1 evidence that this additional pressure monitoring on the lumbar drain guarantees safety, beyond its physiologic rationale being sound. If performed, it requires expertise and caution and it prohibits a permanent CSF diversion at a certain height. Rather, it is required to open the drain on demand and close it during the rest of the time to ensure adequate monitoring (Fig. 2). In the EARLYDRAIN protocol, stopping lumbar CSF diversion in case of ICP levels higher than 20 mmHg is the recommended action, regardless of the cerebrospinal gradient.
OPEN QUESTIONS The results of the EARLYDRAIN study need to be awaited before more definite recommendations may be given. If warranted at all, it is plausible that application of lumbar drains should be restricted for high-grade patients and spared in patients with less risk for delayed cerebral ischemia. One advantage of lumbar drains in SAH may be decreasing the incidence of posthemorrhagic hydrocephalus. Available evidence from the retrospective case series as well as the prospective LUMAS study is inconclusive. Both retrospective cohort series specified 5–10 ml/h of drainage via the lumbar route but remained silent on the actual amount of CSF drained. LUMAS reported an average drainage rate of 138 ml/24 h and a median duration of 5 days. For
safety reasons and to homogenize treatment, the EARLYDRAIN protocol restricts drainage via the lumbar route to 5 ml/h and requires, if necessary, additional drainage via an external ventricular drain for the first 8 days after hemorrhage. Investigation of different drainage regimens, as well as possible administration of fibrinolytics, will be worthwhile [34,35].
CONCLUSION A lumbar drainage presents an additional, physiologically appealing treatment concept for patients after aneurysmal SAH. However, so far, no conclusive evidence is available from retrospective data and the only large high-quality prospective trial failed to prove a better neurologic outcome at 6 months. Concerns about the safety of lumbar drains are not backed up by existing literature, but neither is early adoption in existing treatment algorithms. Therefore, at present, no definite conclusion and recommendation on lumbar drains in patients with SAH is warranted. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest The author is the Senior Investigator of the EARLYDRAIN trial.
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REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Prabhakaran S, Fonarow GC, Smith EE, et al. Hospital case volume is associated with mortality in patients hospitalized with subarachnoid hemorrhage. Neurosurgery 2014; 75:500–508. 2. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002; 360:1267–1274. 3. Macdonald RL, Higashida RT, Keller E, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke J Cereb Circ 2012; 43:1463–1469. 4. Macdonald RL, Higashida RT, Keller E, et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol 2011; 10:618–625. 5. Kreiter KT, Rosengart AJ, Claassen J, et al. Depressed mood and quality of life after subarachnoid hemorrhage. J Neurol Sci 2013; 335:64–71. 6. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980; 6:1–9. 7. Claassen J, Bernardini GL, Kreiter K, et al. Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke J Cereb Circ 2001; 32:2012–2020. 8. Wilson DA, Nakaji P, Abla AA, et al. A simple and quantitative method to predict symptomatic vasospasm after subarachnoid hemorrhage based on computed tomography: beyond the Fisher scale. Neurosurgery 2012; 71:869–875. 9. Komotar RJ, Zacharia BE, Otten ML, et al. Controversies in the endovascular management of cerebral vasospasm after intracranial aneurysm rupture and future directions for therapeutic approaches. Neurosurgery 2008; 62:897– 905. 10. 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; 111:147–154. 11. McDougall CG, Spetzler RF, Zabramski JM, et al. The barrow ruptured aneurysm trial. J Neurosurg 2012; 116:135–144. 12. 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; 28:56–59. 13. Widenka DC, Wolf S, Schu¨rer L, et al. Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurol Neurochir Pol 2000; 34: 56–60. 14. Klimo P, Kestle JRW, MacDonald JD, et al. Marked reduction of cerebral && vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 2004; 100:215–224. A retrospective study that illustrates the concept of lumbar drains in aneurysmal SAH and shows convincing data concerning improvement of outcome. 15. Maeda Y, Shirao S, Yoneda H, et al. Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg 2013; 115:965–970. 16. Ormond DR, Dressler A, Kim S, et al. Lumbar drains may reduce the need for permanent CSF diversion in spontaneous subarachnoid haemorrhage. Br J Neurosurg 2013; 27:171–174.
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17. Kwon OY, Kim Y-J, Kim YJ, et al. The utility and benefits of external lumbar CSF drainage after endovascular coiling on aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc 2008; 43:281–287. The second most important retrospective study, dealing with patients after coiling. 18. Tizi K, Gu¨resir E, Beck J, et al. The effect of lumbar drainage on cerebral vasospasm and infarction after subarachnoid haemorrhage (abstract). 60th Annual Meeting of the German Society of Neurosurgery (DGNC) 2009; Mu¨nster, Germany. 19. Hoekema D, Schmidt RH, Ross I. Lumbar drainage for subarachnoid hemorrhage: technical considerations and safety analysis. Neurocrit Care 2007; 7:3–9. 20. Al-Tamimi YZ, Bhargava D, Feltbower RG, et al. Lumbar drainage of cerebrosp&& inal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS). Stroke J Cereb Circ 2012; 43:677–682. The only high-quality prospective trial on lumbar drains. This is at present the best evidence available. First results in a less severely affected patient population are negative, though. 21. Rankin J. Cerebrovascular accidents in patients over the age of 60: prognosis. Scott Med J 1957; 2:200–215. 22. Ha¨nggi D, Eicker S, Beseoglu K, et al. A multimodal concept in patients after severe aneurysmal subarachnoid hemorrhage: results of a controlled single centre prospective randomized multimodal phase I/II trial on cerebral vasospasm. Cent Eur Neurosurg 2009; 70:61–67. 23. Sun C, Du H, Yin L, et al. Choice for the removal of bloody cerebrospinal fluid in postcoiling aneurysmal subarachnoid hemorrhage: external ventricular drainage or lumbar drainage? Turk Neurosurg 2014; 24:737–744. 24. Borkar SA. 183 spinal cerebrospinal fluid drainage for prevention of vasospasm in aneurysmal subarachnoid haemorrhage: a prospective randomized controlled study. Neurosurgery 2013; 60:180–181. 25. Bardutzky J, Witsch J, Ju¨ttler E, et al. EARLYDRAIN – outcome after early lumbar CSF-drainage in aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial. Trials 2011; 12:203. 26. Staykov D, Speck V, Volbers B, et al. Early recognition of lumbar overdrainage & by lumboventricular pressure gradient. Neurosurgery 2011; 68:1187–1191. This article illustrates the concept of cerebrolumbar pressure gradients, which may present an important tool for safe lumbar drainage in patients with high-grade SAH. 27. Wang K, Liu Z, Chen X, et al. Clinical characteristics and outcomes of patients with cerebral herniation during continuous lumbar drainage. Turk Neurosurg 2013; 23:653–657. 28. 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; 110:1200–1208. 29. Abulhasan YB, Al-Jehani H, Valiquette M-A, et al. Lumbar drainage for the treatment of severe bacterial meningitis. Neurocrit Care 2013; 19:199–205. 30. Murad A, Ghostine S, Colohan AR. A case for further investigating the use of controlled lumbar cerebrospinal fluid drainage for the control of intracranial pressure. World Neurosurg 2012; 77:160–165. 31. Knol DS, van Gijn J, Kruitwagen CLJJ, et al. Size of third and fourth ventricle in obstructive and communicating acute hydrocephalus after aneurysmal subarachnoid hemorrhage. J Neurol 2011; 258:44–49. 32. Kawahara I, Tsutsumi K, Matsunaga Y, et al. Early awareness of cerebrospinal fluid hypovolemia after craniotomy for microsurgical aneurysmal clipping. Acta Neurochir (Wien) 2013; 155:1543–1548. 33. Speck V, Staykov D, Huttner HB, et al. Lumbar catheter for monitoring of intracranial pressure in patients with posthemorrhagic communicating hydrocephalus. Neurocrit Care 2011; 14:208–215. 34. Ramakrishna R, Sekhar LN, Ramanathan D, et al. Intraventricular tissue plasminogen activator for the prevention of vasospasm and hydrocephalus after aneurysmal subarachnoid hemorrhage. Neurosurgery 2010; 67:110–117. 35. Gerner ST, Kuramatsu JB, Abel H, et al. Intraventricular fibrinolysis has no effects on shunt dependency and functional outcome in endovascular-treated aneurysmal SAH. Neurocrit Care 2014; 21:435–443. &
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