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 Table of Contents  
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 76-79

Adenosine in facilitating aneurysm clipping: An institutional experience

Department of Neurosurgery, Velammal Medical College, Madurai, Tamil Nadu, India

Date of Submission04-Jan-2022
Date of Decision10-Jan-2022
Date of Acceptance14-Jan-2022
Date of Web Publication5-Apr-2022

Correspondence Address:
Dr. Ganesh Kumar Manoharan
Department of Neurosurgery, Velammal Medical College, Madurai, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcvs.jcvs_3_22

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Introduction: Intracranial aneurysms are the one of most complicated conditions confronted by a neurosurgeon. Even though endovascular procedure is preferred, open surgery and clipping of the aneurysm still remains gold standard procedure for many aneurysms. Proximal control of the parent vessel remains one of the most critical steps in clipping the aneurysms and this can be achieved by various ways such as temporary clipping and transient cardiac standstill using adenosine. Temporary clipping is associated with complications such as infarct and injury to the vessel, whereas temporary hypotension using adenosine provides a way for successful clipping of the aneurysm. Here, we present our experience with adenosine in patients undergoing clipping of aneurysms in our institution between 2017 and 2020.
Methodology: It is a retrospective cohort study conducted on patients undergoing craniotomy and clipping of aneurysms and in those where adenosine is not contraindicated. Patients are divided into Group A where adenosine is not used and Group B where adenosine is used.
Results: In Group B, where adenosine is used, clipping was easier, with less incidence of intraoperative ruptures, less usage of Temporary clip (TC) and less incidence of infarct, reduce clipping time with no side effects.
Conclusion: Adenosine-induced transient cardiac arrest and hypotension are a safe and effective method in facilitating aneurysm clipping.

Keywords: Adenosine-induced cardiac arrest, intracranial aneurysms, temporary clipping

How to cite this article:
Manoharan GK, Prasad R J, Kumar S, Arvind K R. Adenosine in facilitating aneurysm clipping: An institutional experience. J Cerebrovasc Sci 2021;9:76-9

How to cite this URL:
Manoharan GK, Prasad R J, Kumar S, Arvind K R. Adenosine in facilitating aneurysm clipping: An institutional experience. J Cerebrovasc Sci [serial online] 2021 [cited 2022 Aug 14];9:76-9. Available from: http://www.jcvs.com/text.asp?2021/9/2/76/342561

  Introduction Top

Cerebral aneurysms are one of the complicated neurosurgical conditions and carry high mortality when ruptured. It warrants highest surgical skills and advanced intensive care in treating these conditions. During the surgery of cerebral aneurysm, it is very important to properly dissect the neck of aneurysm to achieve complete occlusion of aneurysm. However, aneurysm has variable anatomy, and sometimes, it becomes difficult to clip an aneurysm without temporarily decompressing it. This can be achieved by obtaining proximal control either by temporary clipping or by transient cardiac asystole using adenosine. Our study aims at highlighting the usefulness of adenosine in clipping of various aneurysms.

Pharmacology of adenosine

Adenosine is a nucleoside analogue that binds to cardiac A1 receptors, which are membrane G-protein-coupled receptors which causes activation of adenylyl cyclase and thus decreasing intracellular cyclic adenosine monophosphate and decreased inward calcium conductance.<sup> [1,2]</sup> It depresses sinoatrial (SA) node activity (negative chronotropic effect) which results in decreases atrioventricular (AV) nodal conduction (negative dromotropic effect) and atrial contractility and ventricular automaticity.<sup>[2]</sup> The effect starts after 12–20 s after bolus injection which causes transient hypotension and decreased mean arterial pressure (MAP).<sup>[3]</sup> Because of its rapid onset and offset, a bolus of adenosine can allow a transient asystole with temporary hypotension that decompresses the aneurysm sac and improves visualisation without the negative effects of prolonged hypotension.

  Methodology Top

It is a retrospective cohort study which consists of two groups, Group A where no adenosine is being used and Group B where adenosine is used to achieve transient cardiac asystole. Perioperative records of all the patients were reviewed. Adenosine 18–30 mg was used to achieve transient bradycardia and asystole for around 1530 s. The median dose for a single bolus was 24 mg. The median total dose of multiple boluses was 60 mg (range 30–150 mg). The median number of boluses was 3 (range 2–10). No adenosine-related complications like conduction abnormalities were noted intraoperatively. The following results were observed.

  Results Top

Each group consisted 25 patients [Table 1]. In Group A, 15 were males and 10 females, and in Group B, they were 14 and 11, respectively. The mean age of patients in Group A and Group B is 55.86 and 51.72, respectively. Most of the cases presented with World Federation of Neurosurgical Societies (WFNS) Grade 2 state, i.e.,48% and 60% in Group A and Group B, respectively.
Table 1: Demographic details of the patients

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Characteristics of aneurysms

Amongst Group A, 22 aneurysms were in anterior circulation and 3 were in posterior circulation, whereas in Group B, there were 19 and 6 in anterior and posterior circulation, respectively. Most of them were small by size, and the mean neck size in Group A and Group B is 4.8 and 4.6, respectively. There were no significant differences between the groups in age, Fisher grade at presentation, median aneurysm size, rupture status and aneurysm location [Table 2].
Table 2: Characteristics of aneurysm in study group

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On analysis and comparing both the groups, the following results were observed [Table 3].
Table 3: Observations in both study groups

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Our study demonstrates that in Group B, where adenosine is used, minimises the usage of temporary clips. In Group A where adenosine is not used, TC was used in 21 cases compared to 12 cases in Group B, and frequency of TC was used. It also facilitates clipping of aneurysms with very less incidence of intraoperative ruptures. Post-operative incidence of iatrogenic infarcts also reduces drastically with adenosine. One of the major complications, vasospasm, is less when adenosine is used. This collates with study conducted by Chris Woertgen et al. which concluded that it seems possible that temporary vessel occlusion is an additional factor in aggravating vasospasm after aneurysmatic subarachnoid haemorrhage.

A Chi-square test was performed to examine the difference in proportion of surgeries where temporary clip (s) was used. Adenosine can induce transient cardiac standstill and fall in MAP and thus helps in avoiding usage of TC. The Chi-square (4, N = 50) = 7.22, P value is significant at. 007 (alpha level 0.05) [Table 4].
Table 4: Comparison of use of temporary clips in both groups

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On testing for difference in proportion of surgeries where there were intraoperative ruptures reported, it was found that the odds of intraoperative ruptures reported were 6.47 times lower if adenosine is used [Table 5].
Table 5: Comparison of intraoperative ruptures in both groups

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The mean number of times temporary clips applied in Group A was higher (3.08) than that in Group B (1.96). This difference across groups was found to be statistically significant on conducting a t-test, with P value at 0.001 [Table 6].
Table 6: Statistical difference and significance in use of temporary clips in both groups

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  Discussion Top

Adenosine induces temporary cardiac asystole and reduces MAP which facilitates aneurysmal decompression and thus helps the surgeon to dissect it and for proper application of the clip. In 1984, Sollevi et al.<sup>[4]</sup> studied ten patients undergoing aneurysm surgery. An adenosine infusion of 0.14 mg/kg/min leads to a decrease in MAP by 43% (82 to 46 mmHg) and a mean hypotensive period of 32 min, without signs of tachyphylaxis. In 1987, Owall et al. studied 47 patients (46 undergoing aneurysmal clip ligation and 1 arteriovenous malformation (AVM) resection). Adenosine was infused, starting at 0.04 mg/kg/min and increasing by 0.04 every 30 s until a desired MAP of 40–50 mmHg was reached (range: 0.088–0.530 mg/kg/min).

While Sollevi et al. and Owall et al. used adenosine infusions,<sup> [4,5]</sup> more recently, adenosine boluses have been implemented for cardiac arrest. In 1999, Groff et al.<sup>[6]</sup> reported the first use of adenosine bolus to clip an un-ruptured basilar tip aneurysm in one patient. In this study, the authors used concomitant infusion of sodium NP and gave three doses of adenosine: 6 mg, then 12 mg and then another 12 mg, which caused 8–13 s of profound hypotension (MAP ~15 mmHg) and allowed the safe and successful placement of a clip. In 2010, Powers et al. used adenosine by bolus for clipping anterior circulation aneurysms in six patients, administering escalating doses until 30 s of asystole was achieved (6 mg, 12 mg, 18 mg, 24 mg and 36 mg). They found a rate of 1-mg adenosine resulting in 1 s of asystole on average.<sup>[1]</sup>

While temporary clipping is a valuable tool, it cannot be applied in all cases. This is especially true for large or deep aneurysms in narrow corridors or near the skull base where temporary clip ligation can further obscure a limited view or is even entirely impossible and if there is atherosclerotic parent vessel where obtaining a proximal control becomes difficult. In these situations, adenosine-induced cardiac arrest relaxes the brain and may improve visualisation in narrow corridors.<sup>[7]</sup> Moreover, temporary clip ligation only decreases blood flow from one direction, while adenosine-induced hypotension is more global and, in certain instances, can more effectively decompress the aneurysmal dome.<sup>[8]</sup>

Even though there are no absolute indications for adenosine, adenosine is safe and effective in the above-mentioned situations. There are very few absolute contraindications to use adenosine [Table 7].
Table 7: Indications and contraindications for adenosine use

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The maximum safe time limit for temporary clipping is around 10–15 mins in most of the studies beyond which it may lead to focal iatrogenic ischaemia.<sup>[9]</sup> If circulation arrest is needed for a brief period, say around 4 mins, adenosine-induced hypotension can be very good alternative to avoid complications due to temporary clipping.


Adenosine is safe and effective drug for temporary cardiac asystole with very rare complications in almost all the studies. Very few cases of cardiac arrhythmias have been reported which were transient with no long-term complications.<sup>[10-12]</sup> Kahn et al. report a case series on endovascular aortic aneurysm repair using an initial dose of 24 mg that was escalated until 10 s of asystole occurred. They observed a 9% incidence of mild cardiac complication, 2% incidence of self-limited ST depression, 2% atrial fibrillation requiring cardioversion, 1% transient left bundle branch block lasting <10 s and 4% temporary heart block requiring pacing for <30 s. They had no cases of bronchospasm or worsening obstructive pulmonary disease.<sup>[13]</sup>

  Conclusion Top

Adenosine-induced transient cardiac arrest is extremely useful as a adjuvant or alternative to temporary clipping. Is effect facilitates aneurysm dissection and clipping and it also reduces requirement of temporary clips and thus reduces incidence of infarcts or vasospasm. It is also found that adenosine has very fewer side effects and does not increase the risk of cardiac arrhythmias or myocardial infarction.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Powers CJ, Wright DR, McDonagh DL, Borel CO, Zomorodi AR, Britz GW. Transient adenosine-induced asystole during the surgical treatment of anterior circulation cerebral aneurysms: Technical note. Neurosurgery 2010;67:461-70.  Back to cited text no. 1
Makaryus JN, Catanzaro JN, Friedman ML, Katona KC, Makaryus AN. Persistent second-degree atrioventricular block following adenosine infusion for nuclear stress testing. J Cardiovasc Med (Hagerstown) 2008;9:304-7.  Back to cited text no. 2
Bebawy JF, Gupta DK, Bendok BR, Hemmer LB, Zeeni C, Avram MJ, et al. Adenosine-induced flow arrest to facilitate intracranial aneurysm clip ligation: Dose response data and safety profile. Anesth Analg 2010;110:1406-11.  Back to cited text no. 3
Sollevi A, Lagerkranser M, Irestedt L, Gordon E, Lindquist C. Controlled hypotension with adenosine in cerebral aneurysm surgery. Anesthesiology 1984;61:400-5.  Back to cited text no. 4
Owall A, Gordon E, Lagerkranser M, Lindquist C, Rudehill A, Sollevi A. Clinical experience with adenosine for controlled hypotension during cerebral aneurysm surgery. Anesth Analg 1987;66:229-34.  Back to cited text no. 5
Groff MW, Adams DC, Kahn RA, Kumbar UM, Yang BY, Bederson JB. Adenosine-induced transient asystole for management of a basilar artery aneurysm. Case report. J Neurosurg 1999;91:687-90.  Back to cited text no. 6
Heppner PA, Ellegala DB, Robertson N, Nemergut E, Jaganathan J, Mee E. Basilar tip aneurysm adenosine induced asystole for the treatment of a basilar tip aneurysm following failure of temporary clipping. Acta Neurochir (Wien) 2007;149:517-20.  Back to cited text no. 7
Britz GW. Adenosine-induced transient asystole. Methodist Debakey Cardiovasc J 2014;10:220-3.  Back to cited text no. 8
Lavine SD, Masri LS, Levy ML, Giannotta SL. Temporary occlusion of the middle cerebral artery in intracranial aneurysm surgery: Time limitation and advantage of brain protection. J Neurosurg 1997;87:817-24.  Back to cited text no. 9
Bebawy JF, Gupta DK, Bendok BR, Hemmer LB, Zeeni C, Avram MJ, et al. Adenosine-induced flow arrest to facilitate intracranial aneurysm clip ligation: Dose-response data and safety profile. Anesth Analg 2010;110:1406-11.  Back to cited text no. 10
Rangel-Castilla L, Russin JJ, Britz GW, Spetzler RF. Update on transient cardiac standstill in cerebrovascular surgery. Neurosurg Rev 2015;38:595-602.  Back to cited text no. 11
Bendok BR, Gupta DK, Rahme RJ, Eddleman CS, Adel JG, Sherma AK, et al. Adenosine for temporary flow arrest during intracranial aneurysm surgery: A single-center retrospective review. Neurosurgery 2011;69:815-20.  Back to cited text no. 12
Kahn RA, Moskowitz DM, Marin ML, Hollier LH, Parsons R, Teodorescu V, et al. Safety and efficacy of high-dose adenosine-induced asystole during endovascular AAA repair. J Endovasc Ther 2000;7:292-6.  Back to cited text no. 13


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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