Intraoperative rupture (IOR) of an intracranial aneurysm is a complication with devastating clinical results. It occurs in up to 60%,1 during open surgery, and 2% to 5% during in endovascular embolization. Despite the lower incidence of the latter, mortality is of concern.2
The development of microneurological surgery has made open surgery a safer technique with better results due to the minimal damage caused. IOR can occur during exposure, dissection, or clipping. The neurosurgeon may opt for proximal temporal occlusion of the vessel, decreasing the turgidity of the aneurysm and improving the visualization of the neck to reduce the risk.3 Yet, this option remains a challenge when visualization of the proximal artery is difficult because of its location and in the case of giant aneurysms.4
An adenosine-induced circulatory arrest facilitates temporary clipping in these cases, even serving as an alternative to it before final clipping.5–7
Although the available literature has shown it to be a safe and effective technique, here, we report a complication risk in relation to the use of multiple doses.
A 58-year-old female, mestizo, from the Peruvian highlands (2720 masl), with a history of poorly controlled arterial hypertension.
Four months before entering our hospital, she presents an subarachnoid hemorrhage (computerized tomography, Fisher grade 3) and receives conservative management at her local hospital. She was admitted at our hospital with a World Federation of Neurosurgical Societies (WFNS) scale grade 1, and underwent an angiotomography with 3D reconstruction that revealed 7 intracranial aneurysms, 3 on the left side (left posterior communicator [the one that bled], left internal carotid and M1 segment of the left midbrain), and 4 on the right side (right anterior choroid, right posterior communicator, A1 segment of the right anterior cerebral, right midbrain bifurcation).
Clipping surgery is scheduled with open microsurgical technique and adenosine is anticipated in coordination with the neurosurgical team.
Five-lead electrocardiogram, pulse oximetry, temperature, and invasive blood pressure (BP) were monitored. Transcutaneous electrical stimulation patches were placed as a safety measure. Induction and maintenance were performed with propofol, fentanyl, and vecuronium.
After positioning, 2 supraorbital craniotomies were performed on each side for sequential clipping of the aneurysms. Adenosine was used 3 times to promote temporal clipping of the proximal artery in the larger aneurysms.
With 110/60 mm Hg BP and 65 bpm heart rate (HR), an initial bolus of adenosine (18 mg) is administered, achieving asystole for 30 seconds with subsequent recovery of sinus rhythm and renewal of hemodynamics. A second dose was administered 25 minutes later, obtaining asystole for 35 seconds, with spontaneous recovery. The third dose was administered after 30 minutes, achieving asystole for 30 seconds with immediate onset of atrial fibrillation (AF) associated with persistent deep hypotension (Table 1). Electric cardioversion is decided with 100 J, returning sinus rhythm with 75 lpm HR and 95/60 mm Hg BP. There were no more incidents. Total bleeding was 350 cm3.
Once the surgery is over, the patient goes to the intensive care unit (ICU) in optimal conditions for extubation and postoperative control. Postsurgery electrocardiogram (ECG) and cardiac enzymes were normal. Discharge from ICU was within 24 hours without complications or deficits. Currently, the patient has no cardiological or neurological sequelae.
The report could be about the case with most surgically treated aneurysms in a single intervention.8
In the presence of 3 large aneurysms at risk of rupture, adenosine was used to soften the aneurysms and improve visualization of the neck.
Adenosine is a nucleoside that binds to the A1 receptor at myocardial level, producing negative chronotropism and dromotropism. It also inhibits atrioventricular conduction and prolongs the refractory period.9
Adenosine has been used for 30 years in the treatment of supraventricular tachycardias (0.05–0.1 mg/kg). During surgery, its use dates from 1989, being administered initially as infusion to achieve a sustained hypotension, and later, in high-dose boluses to achieve transitory asystolia.7
Bebawy et al found that a dose of 0.34 mg/kg (0.29–0.44 mg/kg) achieved systolic BP < 60 mm Hg for 57 seconds (29–105 seconds).10 With similar results, Guin et al11 found that after a dose of 0.24 to 0.42 mg/kg, a drop in systolic BP (<60 mm Hg) and bradycardia (<40 bpm) was achieved for 30 to 60 seconds. In our patient the dose used was 0.3 mg/kg, similar to the mentioned series. However, deep hypotension lasted 30 seconds on average.
The administration of adenosine for these purposes is a safe and effective technique; as is demonstrated by Bendok et al in a retrospective work that included 40 patients, where only 2 presented significant postoperative Troponin elevation, both without clinical or echocardiographic record to support acute myocardial alteration. In addition, 5 of the patients included presented transient arrhythmias: 2 with atrial fibrillation, which reversed spontaneously, and 3 with sinus tachycardia and bradycardia in the postoperative period, which reversed completely.12 Luostarinen et al13 after analyzing a series of 16 cases, found no early or late adverse events after adenosine administration.
In a comparative retrospective study, Khan et al14 found no differences in the incidence of heart complications and 30-day mortality, whether or not adenosine was used.
Repeated doses are possible because adenosine does not cause rebound hypertension or tachyphylaxis. Groff et al15 reported a case in which they used triple doses of adenosine, without complications, for clipping a basilar artery anerurysm. Heppner et al16 also reported a case of basilar aneurysm administering triple dose, where the death of the patient was not due to adenosine.
In the study by Guinn et al11, 1 of 27 patients presented prolonged arterial hypotension (5.5 min), requiring chest compressions, after a rapid redose of adenosine without interdose recovery. Deb et al17 reported a case in which after a second dose, 22 minutes after the first dose, and with previous bleeding of 1.5 L, the patient developed supraventricular tachycardia which progressed to atrial fibrillation with persistent hypotension. This report partially coincides with our finding, with the difference that the complication appeared after a third dose, with an interdose interval of approximately 30 minutes and without significant previous bleeding.
Other studies where more than 1 dose was used have not demonstrated complications.5,10–13
The proarrhythmic potential of adenosine can lead to ventricular and supraventricular tachycardias. AF is the most common one, and may be associated with hemodynamic collapse.18 As in our case, such situations require electrical cardioversion, so the stimulation patches should be placed before surgery and anti-arrhythmic drugs should be available.
There is evidence in aortic aneurysm repair that adenosine may trigger transient changes in the ST segment.19 This complication has not been reported in intracranial aneurysm surgery; however, it is appropriate to follow-up postoperatively with electrocardiogram controls and cardiac enzymes.
Adenosine has been proven to be effective and safe in aneurysm surgery; however, its use should be planned from the pre-operative stage and possible cardiological complications should be considered.
The possible use of adenosine should be planned from the pre-operative stage to anticipate possible scenarios.
More extensive studies are recommended to assess the safety of adenosine.
The patient's perspective: The patient knew the magnitude of her illness and the possible strategies from the pre-operative stage. The results were satisfactory. She currently carries out her activities as before, with no sequelae associated to the treatment.
Protection of humans and animals: The authors state that no human or animal experiments have been carried out for this research.
Data confidentiality: The authors state that they have followed their workplace protocols on the publication of patient data.
Right to privacy and informed consent: The authors state that no patient data appears in this article. The patient freely gave informed consent.
Authors did not receive sponsorship to carry out this article.
Conflict of interest
The authors declare that they have no conflict of interest.
1. Fridriksson S, Saveland H, Jakobsson KE, et al. Intraoperative complications in aneurysm surgery: a prospective national study. J Neurosurg
2. Tummala RP, Chu RM, Madison MT, et al. Outcomes after aneurysm ruptura during endovascular coil embolization. Neurosurgery
3. Schuette AJ, Barrow DL, Cohen-Gadol AA. Strategies to minimize complications during intraoperative aneurysmal hemorrhage: a personal experience. World Neurosurg
4. Ferch R, Pasqualin A, Pinna G, et al. Temporary arterial occlusion in the repair of ruptures intracranial aneurysms: an analysis of risk factors for stroke. J Neurosurg
5. Lee SH, Kwun BD, Kim JU, et al. Adenosine
-induced transient asystole during intracranial aneurysm
surgery: indications, dosing, efficacy, and risks. Acta Neurochir
6. Chowdhury T, Petropolis A, Wilkinson M, et al. Controversies in the anesthetic management of intraoperative rupture of intracranial aneurysm
. Anesth Res Pract
7. Khan SA, Nimjee SM, Guinn NN, et al. The use of adenosine
in cerebral aneurysm clipping: a review. Curr Anesthesiol Rep
8. Choque-Velasquez J, Colasanti R, Fotakopoulos G, et al. Seven cerebral aneurysms: a challenging case from the Andean slopes managed with 1-stage surgery. World Neurosurg
9. Layland J, Carrick D, Lee M, et al. Adenosine
: physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv
10. Bebawy JF, Gupta DK, Bendok BR, et al. Adenosine
-induced flow arrest to facilitate intracranial aneurysm
clip ligation: dose-response data and safety profile. Anesth Analg
11. Guinn NR, McDonagh DL, Borel CO, et al. Adenosine
-induced transient asystole for intracranial aneurysm
surgery. A restrospective review. J Neurosurg Anesthesiol
12. Bendok BR, Gupta DK, Rahme RJ, et al. Adenosine
for temporary flow arrest during intracranial aneurysm
surgery: a single-center retrospective review. Neurosurgery
13. Luostarinen T, Takala RS, Niemi TT, et al. Adenosine
-induced cardiac arrest during intraoperative cerebral aneurysm ruptura. Word Neurosurg
14. Khan SA, McDonagh DL, Adogwa O, et al. Perioperative cardiac complications and 30-day mortality in patients undergoing intracranial aneurysmal surgery with adenosine
-induced flow arrest: a retrospective comparative study. Neurosurgery
15. Groff MW, Adams DC, Kahn RA, et al. Adenosine
-induced transient asystole for management of a basilar artery aneurysm. Case report. J Neurosurg
16. Heppner PA, Ellegala DB, Robertson N, et al. Basilar tip aneurysm – adenosine
induced asystole for the treatment of a basilar tip aneurysm following failure of temporary clipping. Acta Neurochir (WIen)
17. Deb K, Ghosh J, Jain H, et al. Adenosine
in difficult aneurysm surgeries: report of two cases. J Neuroanaesthesiol Crit Care
18. Mallet M. Proarrhythmic effects of adenosine
: a review of the literature. Emerg Med J
19. Kahn RA, Moskowitz DM, Marin ML, et al. Safety and efficacy of high-dose adenosine
-induced asystole during endovascular AAA repair. J Endovasc Ther