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• The Authors' response to "Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage"
  Anand Venkatraman, Gyanendra Kumar
  Published on: 19 March 2018
• Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage
  Zhong Yao, Chao You
  Published on: 19 March 2018

• Published on: 19 March 2018

  The Authors' response to "Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage"

  • Anand Venkatraman, Neurologist Massachusetts General Hospital/Brigham and Women's hospital/Harvard Medical School
  • Other Contributors:
    • Gyanendra Kumar, Neurologist

  We appreciate the interest shown by Drs. Yao and You (1) in our paper (2) and find it our pleasure to address their concerns.

  The first point raised by Drs. Yao and You is that our search strategy missed two articles, namely those of Mortimer et al (2015) (3) and Morgan et al (1996) (4). We would like to reassure Drs. Yao and You that we did screen these articles, and decided against including them in our meta-analysis based on our inclusion criteria. The article by Mortimer et al (2015) (3) describes a patient population where balloon angioplasty, verapamil, and papaverine infusions were used separately or in various combinations. They did not break down their results by the specific intra-arterial vasodilator (IAD) used, and therefore we decided not to include this information. The paper by Morgan et al (1996) (4) describes a patient population which overlapped with that described by the same group in another paper, Morgan et al (2000) (5). We had personally communicated with the authors in 2016 regarding the multiple papers from this group, such as Little et al (1994) (6) and Morgan et al (2000)
  (5) that described papaverine infusions for vasospasm. We found out that there were overlaps in these study populations, and that the cohort in the 2000 paper(5) was the most complete. Therefore, only this paper was included in our meta-analysis, while the earlier ones were excluded.

  The second suggestion by Drs. Yao and You was to perform a regression ana...

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  We appreciate the interest shown by Drs. Yao and You (1) in our paper (2) and find it our pleasure to address their concerns.

  The first point raised by Drs. Yao and You is that our search strategy missed two articles, namely those of Mortimer et al (2015) (3) and Morgan et al (1996) (4). We would like to reassure Drs. Yao and You that we did screen these articles, and decided against including them in our meta-analysis based on our inclusion criteria. The article by Mortimer et al (2015) (3) describes a patient population where balloon angioplasty, verapamil, and papaverine infusions were used separately or in various combinations. They did not break down their results by the specific intra-arterial vasodilator (IAD) used, and therefore we decided not to include this information. The paper by Morgan et al (1996) (4) describes a patient population which overlapped with that described by the same group in another paper, Morgan et al (2000) (5). We had personally communicated with the authors in 2016 regarding the multiple papers from this group, such as Little et al (1994) (6) and Morgan et al (2000)
  (5) that described papaverine infusions for vasospasm. We found out that there were overlaps in these study populations, and that the cohort in the 2000 paper(5) was the most complete. Therefore, only this paper was included in our meta-analysis, while the earlier ones were excluded.

  The second suggestion by Drs. Yao and You was to perform a regression analysis to “solve” the heterogeneity. For a methodically sound meta-analysis, heterogeneity is always presumed to exist, as statistical analysis is but one means of measuring it. When statistically significant heterogeneity is found, it should be quantified and accounted for with subgroup and sensitivity analysis, and subsequently potential contributors to it also discussed subjectively. Meta-regression is another step to account for it. Given the relatively small sample sizes and the observational nature of the included studies, we felt a meta-regression would not do justice to the available data, and would be overreaching.
  Finally, they note that several of our studies used balloon angioplasty in addition to IADs, which might have significantly influenced our findings of IAD efficacy and safety. This is a valid concern, which we had anticipated and stated in the limitations section of our manuscript that, “IAD and balloon angioplasty were used in combination in many patients, which may confound our results when the aim was to isolate the effects of IADs”(2). During our data abstraction, we noted that most studies did not separately report data for IADs and balloon angioplasty, and often used these in conjunction. In the interest of retaining sufficient sample sizes for our analysis, we were left with no recourse but to accept even those studies that included balloon angioplasty along with IADs.

  We would once again like to thank Drs. Yao and You for their interest in our paper, and their insightful questions.
  Authors

  References
  1. Yao ZY, C. Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage. Journal of Neurointerventional Surgery. 2017.
  2. Venkatraman A, Khawaja AM, Gupta S, Hardas S, Deveikis JP, Harrigan MR, et al. Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage: a meta-analysis. J Neurointerv Surg. 2017.
  3. Mortimer AM, Steinfort B, Faulder K, Bradford C, Finfer S, Assaad N, et al. The detrimental clinical impact of severe angiographic vasospasm may be diminished by maximal medical therapy and intensive endovascular treatment. J Neurointerv Surg. 2015;7(12):881-7.
  4. Morgan M, Halcrow S, Sorby W, Grinnell V. Outcome of aneurysmal subarachnoid haemorrhage following the introduction of papaverine angioplasty. J Clin Neurosci. 1996;3(2):139-42.
  5. Morgan MK, Jonker B, Finfer S, Harrington T, Dorsch NW. Aggressive management of aneurysmal subarachnoid haemorrhage based on a papaverine angioplasty protocol. J Clin Neurosci. 2000;7(4):305-8.
  6. Little N, Morgan MK, Grinnell V, Sorby W. Intra-arterial papaverine in the management of cerebral vasospasm following subarachnoid haemorrhage. J Clin Neurosci. 1994;1(1):42-6.

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  Conflict of Interest:
  None declared.

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• Published on: 19 March 2018

  Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage

  • Zhong Yao, neurosurgeon Department of Neurosurgery, West China Hospital, Sichuan university, Chengdu, China
  • Other Contributors:
    • Chao You, neurosurgeon

  With great interest, we read the article of Venkatraman et al.[1] published in the Journal of NeuroInterventional Surgery recently. They presented a comprehensive picture depicting the effect of intra-arterial vasodilators (IADs) on the vasospasm following aneurysmal subarachnoid hemorrhage. But we were concerned with several questions weakening the reliability and generalization of the meta-analysis.
  Firstly , though the detailed including criteria and searching strategy were provided in their meta-analysis, at least two eligible studies2,3 were missed which conformed to their including criteria and unfulfilled the excluding criteria. Two cohort studies of Morgan [2] and Mortimer [3] reported the effects of IADs on vasospasm with documentation of interested events, which should be included in Venkatraman’s analysis. Whether addition of these two studies could change the overall effect of IADs was unclear, but including any eligible study was in accordance with PRISMA principle.
  Secondly, owing to the large number of included studies, the heterogeneity was substantial. Venkatraman et al.[1] conducted subgroup and sensitivity analyses, in which the heterogeneity remained significant (most values of I2 greater than 50%). It was rationale to turn to regression analyses in order to find and solve the heterogeneity.
  Besides, this article included studies combining IADs with balloon angioplasty, which might overestimate effectiveness of IADs. IADs w...

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  With great interest, we read the article of Venkatraman et al.[1] published in the Journal of NeuroInterventional Surgery recently. They presented a comprehensive picture depicting the effect of intra-arterial vasodilators (IADs) on the vasospasm following aneurysmal subarachnoid hemorrhage. But we were concerned with several questions weakening the reliability and generalization of the meta-analysis.
  Firstly , though the detailed including criteria and searching strategy were provided in their meta-analysis, at least two eligible studies2,3 were missed which conformed to their including criteria and unfulfilled the excluding criteria. Two cohort studies of Morgan [2] and Mortimer [3] reported the effects of IADs on vasospasm with documentation of interested events, which should be included in Venkatraman’s analysis. Whether addition of these two studies could change the overall effect of IADs was unclear, but including any eligible study was in accordance with PRISMA principle.
  Secondly, owing to the large number of included studies, the heterogeneity was substantial. Venkatraman et al.[1] conducted subgroup and sensitivity analyses, in which the heterogeneity remained significant (most values of I2 greater than 50%). It was rationale to turn to regression analyses in order to find and solve the heterogeneity.
  Besides, this article included studies combining IADs with balloon angioplasty, which might overestimate effectiveness of IADs. IADs worked in coordination with balloon angioplasty, for balloon angioplasty dilated proximal vessel assisting IADs to expand distal vessels. We could not exclude the possibility partial effect on the outcomes was attributable to balloon angioplasty. Similarly, it was reasonable to ascribe many complications to the balloon angioplasty, like vessel perforation.
  In all, we would like to congratulate Venkatraman for the great work of meta-analyzing the impact of IADs on the treatment of vasospasm following subarachnoid hemorrhage.

  References
  1. Venkatraman A, Khawaja AM, Gupta S, et al. Intra-arterial vasodilators for vasospasm following aneurysmal subarachnoid hemorrhage: a meta-analysis. J Neurointerv Surg. 2017.
  2. Morgan M, Halcrow S, Sorby W, Grinnell V. Outcome of aneurysmal subarachnoid haemorrhage following the introduction of papaverine angioplasty. J Clin Neurosci. 1996;3(2):139-142.
  3. Mortimer AM, Steinfort B, Faulder K, et al. The detrimental clinical impact of severe angiographic vasospasm may be diminished by maximal medical therapy and intensive endovascular treatment. Journal of Neurointerventional Surgery. 2015;7(12):881-887.

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  Conflict of Interest:
  None declared.

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