Management of vasospasm seems to be a favourite topic among CICM exmainers. It has come up several times in the past papers and vivas. The following is a list of representative SAQs:
A chapter of Oh's Manual (Ch. 51, pp 568) is the canonic resource for these topics. The gospel of subarachnoid management seems to be this 2012 Guidelines Statement from the AHA. Another good resource is available from Expert Reviews - it is an article from 2015 which lists and discusses all the successfull and unsuccessful trials in this area. The Dabus-Noguiera article quoted in LITFL also offers some opinions about the weirder therapies for AH, such as fasudil, colforsin, IABP, partial aortic occlusion, and so forth.
As far as non-journal study resources go, the LITFL review of vasospasm and DCI is a treatment with satisfying levels of detail; with its authors' interest in neurocritical care being well known, its value is significant as a distillate of his expertise.
For the purpose of this short summary, all these sources have been combined and remixed.
In brief:
These are a selection of the Class I recommendations made by the AHA.
No difference in risk between clipping and coiling.
In detail:
This is a much-spoken-of complication of subarachnoid blood. Generally speaking, 70% of patients will develop this complication.
Firstly, the definitions. They seem to overlap somewhat. And there are thousands of them; just see this table from Nature (2011). Some of the definitions quoted below are derived from proposals made by a multidisciplinary research group, published in Stroke in 2010; others were made by researchers who pined for a clinically relevant definition.
Vasospasm:
Symptomatic vasospasm:
Angiographic vasospasm
Delayed Cerebral Ischaemia (DCI):
Clinical deterioration caused by DCI
In brief, you know it's vasospasm when...
Or, alternatively, there are no symptoms, and your patient is having a silent vasospasm. Therein lies the disadvantage of clinical examination.
There are several techniques of imaging which can be used to recognise vasospasm:
Conventional 4 vessel DSA (Digital Subtraction Angiography):
On DSA assessment, the vasospasm may be graded:
CTA/MRI:
Transcranial Doppler (TCD):
SPECT/PET
Radionuclide scan
EEG:
The classical risk factors are as follows:
A recent analysis of 370 patients has added several more risk factors:
Also: there is no difference in incidence of vasospasm between the clipped group and the coiled group.
That's important to know.
One could (and perhaps one day will) devote a massive excess of attention to this fascinating area.
For now, I will limit myself to quoting LITFL's article by Oliver Flower, which mentions the following:
The reference for this is likely an article by Kolias and Belli from 2008 (Journal of Neuroscience Research).
The BRANT trial from England has demonstrated a massively decreased risk of SAH-induced stroke in patients receiving nimpodipine - they were 34% less likely to develop stroke. One ought to continue nimodipine for 21 days to get the optimal effect. The usue of nimodipine undergoes a more thorough dissection in the following chapter (Evidence for the use of nimodipine in SAH)
This -drug the other calcium channel blocker for vasospasm - also appears to have some sort of cerebral vessel selectivity. Trials from the 1990s support its use as a means of preventing vasospasm; however there was no heroic stroke reduction, and both the treatment and placebo groups had the same outcomes at 3 months. In more recent research focus has shifted to using it intrathecally, or intrarterially, or as a slow-release implant. A 2013 meta-analysis of RCTs (5 of them) has finally found some outcome benefit, but only after combining all the intravenius intrathecal and intraarterial data, which seems like a strange strategy.
Since its debut in 1990, "Triple H" therapy for subarachnoid haemorrhage has been used in ICUs worldwide as a means of protecting the SAH patients from vasospasm-induced stroke.
Hypertension, hypervolaemia, hemodilution. In order to prevent hypoperfusion injury, the prevailing theory was that the blood pressure should be high, the blood volume should be hyperexpanded, and the hematocric should be low (to decrease blood viscosity). This theory seems to have arisen from the simple relationships of fluid dynamics, where pressure gradients and fluid viscosity are the governing determinants of flow rate.
Myburgh has offered this strategy a nice overview in CCR(2005) and couldn’t recommend it on the balance of evidence. Cerebral autoregulation thresholds are too variable among patients, he says, and probably vary regionally among different parts of the cerebral circulation.
Do the experts agree? No of course they do not. Myburg’s opinion is contradicted by Dhar et al, whose prospective physiological study found that Triple H therapy (all three independently) improve cerebral oxygen delivery to vulnerable regions. The debate about this is ongoing. Thus far, the 2009 iteration of the Stroke guidelines for management of SAH has concluded that induced hypertension as part of Triple H therapy is a “reasonable approach”, even though the enthusiastic evidence for its use is far from satisfactory.
The most recent spoonfulls of evidence added into this cauldron have been generally unsupportive of "Triple H" therapy. In 2010, a review of the literature found no evidence to support the use of the full package, or any of its components individually. In 2014, the Japanese have confirmed a lack of improvement in clinical outcdomes in a prospective multicentre study. With such a heterogeneously lumpy porridge of evidence, it is little wonder that a 2014 survey of management protocols has found "striking variability in the practice patterns of European physicians", with 44% of responders using "Triple-H" therapy in spite of the patchiness of the evidence in support of it.
Spilled blood causes vasospasm(it is thought), so one might think that causing a premature breakdown of this blood is beneficial in the prevention of vasospasm. The injection of urokinase followed by some unusual head movements was viewed as a good idea by some Japanese investigators, and had yielded a 50% decrease in vasospasm and associated complications. It is still viewed as an "experimental" therapy.
There was some interest in the idea that statin therapy might somehow decrease the morbidity from subarachnoid haemrorrhage . The STASH trial has compared placebo to an 80mg dose of simvastatin, and was forced to conclude that the findings "do not support a beneficial effect of simvastatin in patients with SAH "
Given the smooth-muscle-relaxing effects of magnesium cations, its application to cerebral vasospasm seems no great logical leap. The MASH-2 trial from 2012 was a multi-center investigation of 64mmol of MgSO4 per day, randomised among 606 patients, which somberly concluded that "intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage".
Clazosentan (a relative of bosentan) is an endothelin-1 receptor antagonist, and it has been investigated in the aptly named Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage (CONSCIOUS-1) trial. The complications of clazosentan therapy (such as anaemia and hypotension) were "manageable". Its use, at least in in severe and moderate vasospasm, demonstrated "a trend toward improvement", as opposed to actual improvement. In short, these drugs only merit the most lukewarm of recommendations.
Nicardipine (as above) has been used intra-arterially to selectively dilate the spasming vessels. Similarly, papaverine ( phosphodiesterase inhibitor) and verapimil (another calcium channel blocker) have been used with some effect, and remain in routine use today. The most recent Critical Care Guidelines on the Endovascular Management of Cerebral Vasospasm have found papaverine to be the most extensively studied agent, and the one with the greatest amount of support behind it; less data exists in support of verapimil and nicardipine. Milrinone has also showed some promise, both as an intrarterial agent and as an inthrathecal irrigation; there may be an additive effect with nimdipine in the setting of refractory vasospasm.
If one does not wish to expose the patient to intraarterial vasodilators, one may instead address the spasm in a very direct and brutally mechanical way, but dilating the spasmed vessel with a balloon. The abovementioned guidelines statement had identified 27 studies. There seems to be some disagreement as to which is better (intraarterial papaverine vs. balloonoplasty studies have a substantial degree of heterogeneity in their reported outcomes). There is no disagreement, however, about the risks - balloons have a known association with arterial rupture and fatal haemorrhage.
Chapter 51 (pp. 568) Acute cerebrovascular complications by Bernard Riley and Thearina de Beer
LITFL offer this reference as a follow-on to their chapter:
Dabus, Guilherme, and Raul G. Nogueira. "Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature." Interventional Neurology 2.1 (2013): 30-51.
Frontera, Jennifer A., et al. "Defining Vasospasm After Subarachnoid Hemorrhage What Is the Most Clinically Relevant Definition?." Stroke 40.6 (2009): 1963-1968.
Vergouwen, Mervyn DI, et al. "Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies Proposal of a Multidisciplinary Research Group."Stroke 41.10 (2010): 2391-2395.
Etminan, Nima, et al. "Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis." Journal of Cerebral Blood Flow & Metabolism 31.6 (2011): 1443-1451.
Brathwaite, Shakira, and R. Loch Macdonald. "Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials." Translational stroke research 5.2 (2014): 207-226.
Mir, D. I. A., et al. "CT Perfusion for detection of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis." American Journal of Neuroradiology 35.5 (2014): 866-871.
Scheglov, Dmitry V., et al. "Endovascular Treatment of Vasospasm Related to Acute Subarachnoid Hemorrhage from Ruptured Aneurysms." Neurovascular Events After Subarachnoid Hemorrhage. Springer International Publishing, 2015. 223-229.
Serrone, Joseph C., et al. "Aneurysmal subarachnoid hemorrhage: pathobiology, current treatment and future directions." Expert review of neurotherapeutics 0 (2015): 1-14.
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Macdonald, R. Loch, et al. "Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1) randomized, double-blind, placebo-controlled Phase 2 dose-finding trial." Stroke39.11 (2008): 3015-3021.
Mees, Sanne M. Dorhout, et al. "Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial." The Lancet380.9836 (2012): 44-49.
Zhang, Shihong, et al. "Tirilazad for aneurysmal subarachnoid haemorrhage."The Cochrane Library (2010).
Liu, Guang Jian, et al. "Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage." European journal of clinical pharmacology 68.2 (2012): 131-139.
Kirkpatrick, Peter J., et al. "Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial." The Lancet Neurology 13.7 (2014): 666-675.
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Connolly, E. Sander, et al. "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association." Stroke 43.6 (2012): 1711-1737.
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Greenberg, E. D., et al. "Diagnostic accuracy of CT angiography and CT perfusion for cerebral vasospasm: a meta-analysis." American Journal of Neuroradiology 31.10 (2010): 1853-1860.
Sloan, M. A., et al. "Sensitivity and specificity of transcranial Doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage." Neurology 39.11 (1989): 1514-1514.
Rivierez, M., et al. "Value of electroencephalogram in prediction and diagnosis of vasospasm after intracranial aneurysm rupture." Acta neurochirurgica 110.1-2 (1991): 17-23.
Kawamoto, Shunsuke, et al. "Effectiveness of the head-shaking method combined with cisternal irrigation with urokinase in preventing cerebral vasospasm after subarachnoid hemorrhage." Journal of neurosurgery 100.2 (2004): 236-243.
Vergouwen, Mervyn DI, et al. "Biologic effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled randomized trial." Journal of Cerebral Blood Flow & Metabolism 29.8 (2009): 1444-1453.
Macdonald, R. Loch, et al. "Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) Randomized, Double-Blind, Placebo-Controlled Phase 2 Dose-Finding Trial."Stroke 39.11 (2008): 3015-3021.
Bakker, Nicolaas A., et al. "International subarachnoid aneurysm trial 2009: endovascular coiling of ruptured intracranial aneurysms has no significant advantage over neurosurgical clipping." Neurosurgery 66.5 (2010): 961-962.
Fisher, C. M., J. P. Kistler, and J. M. Davis. "Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning." Neurosurgery 6.1 (1980): 1-9.
LITFL offer this reference as a follow-on to their chapter:
Dabus, Guilherme, and Raul G. Nogueira. "Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature." Interventional Neurology 2.1 (2013): 30-51.
Frontera, Jennifer A., et al. "Defining Vasospasm After Subarachnoid Hemorrhage What Is the Most Clinically Relevant Definition?." Stroke 40.6 (2009): 1963-1968.
Vergouwen, Mervyn DI, et al. "Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies Proposal of a Multidisciplinary Research Group."Stroke 41.10 (2010): 2391-2395.
Etminan, Nima, et al. "Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis." Journal of Cerebral Blood Flow & Metabolism 31.6 (2011): 1443-1451.
Brathwaite, Shakira, and R. Loch Macdonald. "Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials." Translational stroke research 5.2 (2014): 207-226.
Mir, D. I. A., et al. "CT Perfusion for detection of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis." American Journal of Neuroradiology 35.5 (2014): 866-871.
Lasner, Todd M., et al. "Cigarette smoking-induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage." Journal of neurosurgery 87.3 (1997): 381-384.
Conway, James E., and Rafael J. Tamargo. "Cocaine use is an independent risk factor for cerebral vasospasm after aneurysmal subarachnoid hemorrhage."Stroke 32.10 (2001): 2338-2343.
Charpentier, Claire, et al. "Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage." Stroke30.7 (1999): 1402-1408.
Singhal, A. B., et al. "SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage." Neurology 64.6 (2005): 1008-1013.
Yin, L., et al. "Predictors analysis of symptomatic cerebral vasospasm after subarachnoid hemorrhage." Early Brain Injury or Cerebral Vasospasm. Springer Vienna, 2011. 175-178.
Hussein, Haitham M., et al. "Intracranial Vascular Calcification is Protective from Vasospasm after Aneurysmal Subarachnoid Hemorrhage." Journal of Stroke and Cerebrovascular Diseases (2014).
Inagawa, T., K. Yahara, and N. Ohbayashi. "Risk Factors Associated with Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage."Neurologia medico-chirurgica (2014).
Inagawa, T., K. Yahara, and N. Ohbayashi. "Risk Factors Associated with Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage."Neurologia medico-chirurgica (2014).
Kolias, Angelos G., Jon Sen, and Antonio Belli. "Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: putative mechanisms and novel approaches." Journal of neuroscience research 87.1 (2009): 1-11.
Haley Jr, E. Clarke, Neal F. Kassell, and James C. Torner. "A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage: a report of the Cooperative Aneurysm Study." Journal of neurosurgery 78.4 (1993): 537-547.
Rosenquist, Ashley, et al. "921: Safety of intrathecal nicardipine for vasospasm due to aneurysmal subarachnoid hemorrhage." Critical Care Medicine 41.12 (2013): A231.
Huang, Ren-qiang, et al. "Nicardipine in the treatment of aneurysmal subarachnoid haemorrhage: a meta-analysis of published data." Acta Neurologica Belgica 113.1 (2013): 3-6.
Kasuya, H. "Clinical trial of nicardipine prolonged-release implants for preventing cerebral vasospasm: multicenter cooperative study in Tokyo." Early Brain Injury or Cerebral Vasospasm. Springer Vienna, 2011. 165-167.
Pandey, Paritosh, et al. "A Simplified Method for Administration of Intra-Arterial Nicardipine for Vasospasm With Cervical Catheter Infusion." Neurosurgery 71 (2012): ons77-ons85.
Tagami, Takashi, et al. "Effect of Triple-H Prophylaxis on Global End-Diastolic Volume and Clinical Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage." Neurocritical care (2014): 1-8.
Dankbaar, Jan W., et al. "Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review." Crit Care 14.1 (2010): R23.
Lennihan, Laura, et al. "Effect of Hypervolemic Therapy on Cerebral Blood Flow After Subarachnoid Hemorrhage A Randomized Controlled Trial." Stroke 31.2 (2000): 383-391.
Diringer, Michael N., et al. "Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference." Neurocritical care 15.2 (2011): 211-240.
Velly, Lionel J., et al. "Anaesthetic and ICU management of aneurysmal subarachnoid haemorrhage: A survey of European practice." European journal of anaesthesiology (2014).
Kimball, Matthew M., Gregory J. Velat, and Brian L. Hoh. "Critical care guidelines on the endovascular management of cerebral vasospasm." Neurocritical care 15.2 (2011): 336-341.
Kirkpatrick, Peter J., et al. "Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial." The Lancet Neurology (2014), Volume 13, Issue 7, Pages 666 - 675
Mees, Sanne M. Dorhout, et al. "Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial." The Lancet 380.9836 (2012): 44-49.
Nishiguchi, Mitsuhisa, et al. "Effect of vasodilation by milrinone, a phosphodiesterase III inhibitor, on vasospastic arteries after a subarachnoid hemorrhage in vitro and in vivo: effectiveness of cisternal injection of milrinone." Neurosurgery 66.1 (2010): 158-164.
Anand, Saurabh, Gaurav Goel, and Vipul Gupta. "Continuous intra-arterial dilatation with nimodipine and milrinone for refractory cerebral vasospasm." Journal of neurosurgical anesthesiology 26.1 (2014): 92-93.
Wartenberg, Katja Eliriede, and Stephan A. Mayer. "Intracerebral hemorrhage."The Stroke Book (2013): 204.
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