Nicotine replacement therapy in aneurysmal subarachnoid hemorrhage

Nicotine replacement therapy in aneurysmal subarachnoid hemorrhage

Smoking prevalence is twice as high among patients admitted to hospital because of the acute condition of aneurysmal subarachnoid hemorrhage (aSAH) as in the general population.

Despite vasoactive properties, administration of NRT among active smokers with acute SAH appeared to be safe, with similar rates of vasospasm and DCI, and a slightly higher rate of seizures. The association of NRT with lower mortality could be due to chance, uncontrolled factors, or a neuroprotective effect of nicotine in active smokers hospitalized with SAH, and should be tested prospectively 1).

Smoking was also associated with paradoxical superior outcomes on some measures, and future research to confirm and further understand the basis of this relationship is needed 2).

Current evidence suggests that NRT does not induce vasospasm, and is associated with improved outcomes in smokers hospitalized for SAH. Protocol registered in PROSPERO, available at: 3) 4).

The use of NRT in the acute phase of aSAH does not seem to have an impact on the intensity of headaches or analgesic consumption 5).

Limited safety data may prompt caution regarding seizures and delirium in patients with subarachnoid hemorrhage 6).

Eisenring et al. investigated the international practice of NRT use for aSAH among neurosurgeons.

The online SurveyMonkey software was used to administer a 15-question, 5-min online questionnaire. An invitation link was sent to those 1425 of 1988 members of the European Association of Neurosurgical Societies (EANS) who agreed to participate in surveys to assess treatment strategies for withdrawal of tobacco smoking during aSAH. Factors contributing to physicians’ posture towards NRT were assessed.

A total of 158 physicians from 50 nations participated in the survey (response rate 11.1%); 68.4% (108) were affiliated with university hospitals and 67.7% (107) practiced at high-volume neurovascular centers with at least 30 treated aSAH cases per year. Overall, 55.7% (88) of physicians offered NRT to smokers with aSAH, 22.1% (35) offered non-NRT support including non-nicotine medication and counseling, while the remaining 22.1% (35) did not actively support smoking cessation. When smoking was not possible, 42.4% (67) of physicians expected better clinical outcomes when prescribing NRT instead of nicotine deprivation, 36.1% (57) were uncertain, 13.9% (22) assumed unaffected outcomes, and 7.6% (12) assumed worse outcomes. Only 22.8% (36) physicians had access to a local smoking cessation team in their practice, of whom half expected better outcomes with NRT as compared to deprivation.

A small majority of the surveyed physicians of the EANS offered NRT to support smoking cessation in hospitalized patients with aSAH. However, less than half believed that NRT could positively impact clinical outcomes as compared to deprivation. This survey demonstrated the lack of consensus regarding the use of NRT for hospitalized smokers with aSAH 7).


Seder DB, Schmidt JM, Badjatia N, Fernandez L, Rincon F, Claassen J, Gordon E, Carrera E, Kurtz P, Lee K, Connolly ES, Mayer SA. Transdermal nicotine replacement therapy in cigarette smokers with acute subarachnoid hemorrhage. Neurocrit Care. 2011 Feb;14(1):77-83. doi: 10.1007/s12028-010-9456-9. PMID: 20949331.

Dasenbrock HH, Rudy RF, Rosalind Lai PM, Smith TR, Frerichs KU, Gormley WB, Aziz-Sultan MA, Du R. Cigarette smoking and outcomes after aneurysmal subarachnoid hemorrhage: a nationwide analysis. J Neurosurg. 2018 Aug;129(2):446-457. doi: 10.3171/2016.10.JNS16748. Epub 2017 Oct 27. PMID: 29076779.

Turgeon RD, Chang SJ, Dandurand C, Gooderham PA, Hunt C. Nicotine replacement therapy in patients with aneurysmal subarachnoid hemorrhage: Systematic review of the literature, and survey of Canadian practice. J Clin Neurosci. 2017 Aug;42:48-53. doi: 10.1016/j.jocn.2017.03.014. Epub 2017 Mar 22. PMID: 28342700.

Carandang RA, Barton B, Rordorf GA, Ogilvy CS, Sims JR. Nicotine replacement therapy after subarachnoid hemorrhage is not associated with increased vasospasm. Stroke. 2011 Nov;42(11):3080-6. doi: 10.1161/STROKEAHA.111.620955. Epub 2011 Aug 25. PMID: 21868740.

Charvet A, Bouchier B, Dailler F, Ritzenthaler T. Nicotine Replacement Therapy Does Not Reduce Headaches Following Subarachnoid Hemorrhage: A Propensity Score-Matched Study. Neurocrit Care. 2022 Sep 1. doi: 10.1007/s12028-022-01576-2. Epub ahead of print. PMID: 36050538.

Parikh NS, Salehi Omran S, Kamel H, Elkind MSV, Willey JZ. Smoking-cessation pharmacotherapy for patients with stroke and TIA: Systematic review. J Clin Neurosci. 2020 Aug;78:236-241. doi: 10.1016/j.jocn.2020.04.026. Epub 2020 Apr 22. PMID: 32334957; PMCID: PMC8908464.

Eisenring CV, Hamilton PL, Herzog P, Oertel MF, Jacot-Sadowski I, Burn F, Cornuz J, Schatlo B, Nanchen D. Nicotine Replacement Therapy for Smokers with Acute Aneurysmal Subarachnoid Hemorrhage: An International Survey. Adv Ther. 2022 Sep 19. doi: 10.1007/s12325-022-02300-4. Epub ahead of print. PMID: 3612

UpToDate: Cervical total disc replacement versus anterior cervical discectomy and fusion

Cervical total disc replacement versus anterior cervical discectomy and fusion

Findlay et al., from London and Edinburgh, researched for cervical total disc replacement versus anterior cervical discectomy and fusion.

Databases including Medline, Embase, and Scopus were searched. Inclusion criteria involved prospective randomized control trials (RCTs) reporting the surgical treatment of patients with symptomatic degenerative cervical disc disease. Two independent investigators extracted the data. The strength of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. The primary outcome measures were overall and neurological success, and these were included in the meta-analysis. Standardized patient-reported outcomes, including the incidence of further surgery and adjacent segment disease, were summarized and discussed.

A total of 22 papers published from 14 randomized control trials (RCTs) were included, representing 3160 patients with follow-up of up to ten years. Meta-analysis indicated that TDR is superior to ACDF at two years and between four and seven years. In the short-term, patients who underwent TDR had better patient-reported outcomes than those who underwent ACDF, but at two years this was typically not significant. Results between four and seven years showed significant differences in Neck Disability Index (NDI), 36-Item Short-Form Health Survey (SF-36) physical component scores, dysphagia, and satisfaction, all favouring TDR. Most trials found significantly less adjacent segment disease after TDR at both two years (short-term) and between four and seven years (medium- to long-term).

TDR is as effective as ACDF and superior for some outcomes. Disc replacement reduces the risk of adjacent segment disease. Continued uncertainty remains about degeneration of the prosthesis. Long-term surveillance of patients who undergo TDR may allow its routine use 1).

Cervical total disc replacement (TDR) has been shown in a number of prospective clinical studies to be a viable treatment alternative to anterior cervical discectomy and fusion (ACDF) for symptomatic cervical degenerative disc disease. In addition to preserving motion, evidence suggests that cervical TDR may result in a lower incidence of subsequent surgical intervention than treatment with fusion.

One reason for this trend is the observation that in clinical studies, patients with a history of cervical arthrodesis seem to have a higher incidence of adjacent segment degeneration 2) 3) 4).

Furthermore, in biomechanical investigations, most authors have reported an increase in the segmental range of motion (ROM) and the intradiscal pressure (IDP) in the levels proximal and distal to a simulated mono- or bisegmental arthrodesis 5) 6) 7) 8) 9) 10) 11) 12) 13) 14).

While anterior cervical discectomy and fusion (ACDF) has been the standard of care for 2-level disease, a randomized clinical trial (RCT) suggested similar outcomes.

There are also critical debates regarding the long-term effects of heterotopic ossification (HO) and the prevalence of adjacent-level degeneration.


Findlay C, Ayis S, Demetriades AK. Total disc replacement versus anterior cervical discectomy and fusion. Bone Joint J. 2018 Aug;100-B(8):991-1001. doi: 10.1302/0301-620X.100B8.BJJ-2018-0120.R1. PubMed PMID: 30062947.

Goffin J, Geusens E, Vantomme N, Quintens E, Waerzeggers Y, Depreitere B, et al. Long-term follow-up after interbody fusion of the cervical spine. J Spinal Disord Tech. 2004;17:79–85. doi: 10.1097/00024720-200404000-00001.

Gore DR, Sepic SB. Anterior discectomy and fusion for painful cervical disc disease: a report of 50 patients with an average follow-up of 21 years. Spine. 1998;23:2047–2051. doi: 10.1097/00007632-199810010-00002.

Hilibrand AS, Carlson GD, Palumbo MA, Jones PK, Bohlman H. Radiculopathy and myelopathy at segments adjacent to the site of a previous anterior cervical arthrodesis. J Bone Joint Surg. 1999;81-A:519–528.

Chang U-K, Kim DH, Lee MC, Willenberg R, Kim S-H, Lim J. Changes in adjacent-level disc pressure and facet joint force after cervical arthroplasty compared with cervical discectomy and fusion. J Neurosurg Spine. 2007;7:33–39. doi: 10.3171/SPI-07/07/033.

Chang U-K, Kim DH, Lee MC, Willenberg R, Kim S-H, Lim J. Range of motion change after cervical arthroplasty with ProDisc-C and Prestige artificial discs compared with anterior cervical discectomy and fusion. J Neurosurg Spine. 2007;7:40–46. doi: 10.3171/SPI-07/07/040.

DiAngelo DJ, Foley KT, Morrow BR, Schwab JS, Song J, German JW, et al. In vitro biomechanics of cervical disc arthroplasty with the ProDisc-C total disc implant. Neurosurg Focus. 2004;17(E7):44–54. doi: 10.3171/foc.2004.17.3.7.

DiAngelo DJ, Robertson JT, Metcalf NH, McVay BJ, Davis RC. Biomechanical testing of an artificial cervical joint and an anterior plate. J Spinal Disord Tech. 2003;16:314–323. doi: 10.1097/00024720-200308000-00002.

Dmitriev AE, Cunningham BW, Hu N, Sell G, Vigna F, McAfee PC. Adjacent level intradiscal pressure and segmental kinematics following a cervical total disc arthroplasty. An in vitro human cadaveric model. Spine. 2005;30:1165–1172. doi: 10.1097/01.brs.0000162441.23824.95.

Eck JC, Humphreys SC, Lim T-H, Jeong ST, Kim JG, Hodges SD, et al. Biomechanical study on the effect of cervical spine fusion on adjacent-level intradiscal pressure and segmental motion. Spine. 2002;27:2431–2434. doi: 10.1097/00007632-200211150-00003.

Fuller DA, Kirkpatrick JS, Emery SE. A kinematic study of the cervical spine before and after segmental arthrodesis. Spine. 1998;23:1649–1656. doi: 10.1097/00007632-199808010-00006.

Park D-H, Ramakrishnan P, Cho T-H, Lorenz E, Eck JC, Humphreys SC, et al. Effect of lower two-level anterior cervical fusion on the superior adjacent level. J Neurosurg Spine. 2007;7:336–340. doi: 10.3171/SPI-07/09/336.

Pospiech J, Stolke D, Wilke HJ, Claes LE. Intradiscal pressure recordings in the cervical spine. Neurosurgery. 1999;44:379–384. doi: 10.1097/00006123-199902000-00078.

Ragab AA, Escarcega AJ, Zdeblick TA. A quantitative analysis of strain at adjacent segments after segmental immobilization of the cervical spine. J Spinal Disord Tech. 2006;19:407–410. doi: 10.1097/00024720-200608000-00006.
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