Temporary arterial occlusion (TAO) of vessels during surgical clipping of intracranial aneurysm is an established method that helps in dissection of aneurysms, controlling intra-operative aneurysm rupture (IAR) and helps the surgeon to place a permanent clip precisely at the neck of an aneurysm. However, this may lead to stroke due to impaired cerebral perfusion secondary to temporary occlusion of the feeding arteries [1,21]. Studies suggest that temporary clipping of the major feeding vessels should be broken up by sufficient recirculation time of at least 5 to 10 min when longer periods of arterial occlusion are necessary because ischemic brain damage depends mainly upon the duration of the vessel occlusion [14,19]. On the other hand, experimental studies have documented that repetitive episodes of brief global ischemia may cause cumulative detrimental effects in the form of ischemic neuronal damage, whereas these problems are not seen with a single ischemic episode of the same total duration [22]. These observations are a call to assess cerebral blood flow and perfusion while applying temporary clips to the feeding arteries. There are many direct or indirect ways of assessing cerebral blood flow and perfusion such as intra-operative digital subtraction angiography (DSA), doppler, positron emission tomography (PET), magnetic resonance (MR) perfusion studies, intra-operative and postoperative MR imaging (MRI) with diffusion weighted imaging and somatosensory evoked potential (SSEP). Most of these imaging procedures are technically demanding, expensive and requires additional time and human resources. Intra-operative Doppler, though frequently used, may not provide information regarding flow in the very small vessels as their ability to assess small perforating arteries is poor [4].

Intra-operative Indocyanine green video-angiography (ICG-VA) is a real-time evaluation of intra-operative visualization of parent vessels, perforators and aneurysms, and has an established role to assess the adequacy of clipping of cerebral aneurysms [5]. This study was conducted to study the cerebral blood flow during temporary clipping of aneurysm using ICG-VA and to assess its efficacy.

This study consisted of 122 prospectively enrolled ruptured aneurysm patients who underwent clip ligation during January 2014 to December 2018 using ICG-VA at our institute. Of them, temporary arterial occlusion was utilized in 38 patients with 43 aneurysms. Adult patients of either sex with intracranial aneurysms considered for surgery were included in the study and patients having history of iodine allergy, pregnancy or previous anaphylactic reactions to contrast media or dye injections were excluded. Elective temporary clips were utilized in all cases where neck was found to be calcified or dome contained thrombus to prevent embolic infarct and avoided in cases with atheromatous parent artery. All patients underwent standard microsurgical procedures for clip ligation of their aneurysms assisted by ICG-VA. The Institutional Ethics Committee reviewed and approved this study, and all patients provided consent before participation.

We used the NIR fluorescence module that was integrated into the surgical microscope (Moller Wedel, Germany) to assess the fluorescent areas in the operating field and generate a video of the emitted fluorescent light. Technical principles of ICG as described by Raabe et al. [16] was followed in every patient. The patients received 25 mg intravenous dose of ICG dissolved in 5 mL of 0.9% saline and given as a bolus of 1.5 mL per injection via cephalic vein after doing sensitivity test. Temporary clips were applied to assist dissection and ICG shoots were taken both before and after the temporary clip application to assess the status of branching and perforator arteries. In cases where parent or branching vessel stenosis or residual aneurysm necks were identified with ICG, the clip position was changed or additional clips were applied and another ICG-VA study was performed. Visual assessment of a real time play back of the procedure was performed in every case to note the appearance time of ICG in surgical field. Intra-operative monitoring of systolic blood pressure (SBP), heart rate (HR), pH, hematocrit (Hct), paCO₂ and paO₂ was done throughout the procedure.

MRI brain was performed within 48 hrs in 29 patients before and after the procedure to assess the development of ischemic areas. In poor grade patients, MRI was excluded. Ischemic change from inadvertent vessel occlusion during aneurysm clipping was avoided by assessing ICG-VA post placement of permanent clip and clip was re-adjusted whenever required. Patients were assessed in the postoperative period on the basis of radiological and clinical findings. Radiologic ischemia was defined as having ischemic changes on imaging but no neurologic deficit clinically and symptomatic ischemia was defined as having neurologic deficit as well as ischemic changes on radiologic imaging. Clinical outcome was assessed using modified Rankin Scale (mRS) score 1-month post-surgery. A good outcome was defined as mRS score of 0-2 while poor outcome was defined as mRS score of 3-6. The end points included the occurrence of radiologically documented ischemia on postoperative MRI scans, the development of symptomatic or asymptomatic stroke, and the clinical outcome.

Statistical analyses were done using SPSS 17.0 for windows (SPSS Inc., Chicago, IL, USA) and a p value of less than 0.05 was considered significant. Categorical and continuous variables were compared using the chi-square or Fisher tests and t-test when appropriate. Multivariate logistic regression models were used to analyze factors responsible for ischemic complications and outcome. Relative risk of the variables was obtained by calculating adjusted odds ratios and 95% confidence intervals.

The role of temporary occlusion to control IAR and to facilitate dissection has been well accepted and is used with increasing frequency in the management of intracranial aneurysms. Jefferson was the first to use elective temporary occlusion in 1928 for the treatment of intracranial aneurysms [15]. As the use of TAO during aneurysm surgery is gaining wider acceptance in the neurosurgical practice [2,3,6], it is prudent to define the risks of this procedure as well as to study the hemodynamic changes during its application and to identify a reasonably safe period of occlusion. Ischemia during TAO is difficult to predict and this is where the ICG-VA may play a vital role that may warn the surgeon in the form of diminished fluorescence, delay in appearance or decreased visibility of perforators intraoperatively.

We followed uniform anesthesia regimen in this study with of induction of normothermia and normotension in all cases with initiation of barbiturate infusion before aneurysm clipping in majority of cases. Some studies suggest hypertension or hypothermia during temporary occlusion, while others suggested use of different monitoring techniques to warn the surgeon of impending stroke [13,20]. However, these monitoring techniques remain technically challenging, imperfect and can be misleading [21] and the current study shows that simple assessment of vessel status before and after application of temporary clips is highly useful in predicting impending ischemia.

In our study, the SBP was found to be increased during TAO that remained throughout the application and returned to baseline slowly after its removal. This perhaps may be due to activation of cerebral autoregulation mechanism to maintain flow in vessels distal to occlusion.

Previous studies suggested association of older age with higher risk of stroke and poor outcomes which could probably be afflicted to associated medical conditions like hypertension and vascular diseases seen in elderly leading to greater risk of borderline cerebral perfusion [6,10]. However, current study could not detect any such association. We believe that shorter duration of temporary clips as well as keeping the number of TAO to a minimum possible number has resulted in better outcome in our series. However, more studies and greater number of patients are required to conclusively draw this finding.

Location was not a significant factor for ischemia, but the incidence of symptomatic ischemia was relatively high in patients with DACA aneurysms. We assume it to be due to its technically challenging location and longer duration of dissection requiring more numbers of TAO coupled with minimal cisternal CSF drainage and longer periods of brain retraction.

Timing of surgery is also an important variable for the development of ischemia and thus the outcome. In the acute stages, retraction of the brain parenchyma may lead to reduced perfusion pressure at the local site due to less tolerance which may lead to vasospasm and cerebral dysfunction of immediate or delayed onset [9,18]. Moreover, immediately following SAH, diminished cerebral perfusion develops independent of vasospasm, which also predisposes the patients to stroke. However, the benefits of delayed over early surgical intervention in regard to resistance to ischemia is counteracted by the risks of a wait and watch approach, especially when the overall management of patients with SAH ruptured aneurysms is considered which has also been confirmed by another study [7].

The duration of temporary occlusion remains the most investigated factor in clinical series of patients who undergo TAO [11,13]. In our study, we observed a trend for a decreased incidence of ischemic complication and good outcome in patients in whom temporary vessel occlusion was performed for less than 5 minutes. Furthermore, in our study, patients with repeated TAO, showed a higher incidence of stroke than those with single TAO. There are discordant reports regarding the mode of temporary occlusion [13]. Some authors have claimed that there is a higher risk of ischemia with intermittent occlusion based on the results of experimental studies, whereas others have claimed that the risk is higher when continuous occlusion is performed [11]. The temporary occlusion times reported in the studies in which the rate of ischemia was lower when continuous occlusion was performed and compared with intermittent occlusion also involved substantially longer occlusion times [13]. Previous studies [8,13] have suggested a wide range of safe occlusion time with one recent study [17] suggesting that duration of occlusion of 5 to 7 minutes can be safely tolerated. The current study indicates that even at much lesser duration (~2 min 10 sec), flow starts decreasing in the vessel and perforators distal to occlusion. Multiple application of temporary clip further hampers the flow distal to it. The current study suggests applying shorter duration clips with longer intervals between two clip applications. The number of temporary clips applied should also be cut short to as minimum as possible.

There are certain limitations of the current study. ICG-VA is restricted only to vessels visible in the microscope, but not all perforating arteries may be visible during the moment of ICG-VA. There were cases in which the clip(s) hampered the view and cases with perforating arteries originating from the contralateral wall of the vessel that might have been missed. The manipulation of the vessels during the microdissection procedure and the use of retractors in some cases with subarachnoid hemorrhage, swelling, and intraoperative aneurysm rupture may have led to a temporary compression and occlusion of a perforating artery beyond the ischemic tolerance time. When the retractor is removed or repositioned before ICG-VA, the occluded perforating artery reopens and may thus appear patent during ICG-VA. Another limitation, although unlikely, severe stenosis leading to insufficient flow for the brain perfusion cannot be totally excluded out.

In this study, although Hunt and Hess grade was related to clinical outcome, no significant association could be established between ischemia and Hunt and Hess grade. A previous study, however found significant association of higher Hunt and Hess grade with ischemia [12]. This discrepancy may have resulted from smaller number of cases in our study design.

Patients undergoing clipping for large aneurysms are generally considered to have a poor outcome than patients with small aneurysms as patients with ruptured large aneurysms tend to have a poor clinical condition on admission. However, the current study could not establish any such association. This could again be due to lesser number of patients recruited.

In aneurysm surgery, we often need a combination of different tools and methods to ensure that the aneurysm is occluded and that no vessel is compromised. Therefore, ICG-VA should be considered as one tool among others, such as visual inspection, intraoperative digital subtraction angiography, microvascular doppler and electrophysiological monitoring.

The current study assessed the effect of TAO during aneurysm surgery on hemodynamic parameters and cerebral flow as no previous studies recorded these parameters although use of ICG-VA has now become a norm. The only hemodynamic parameter which showed significant change during TAO is increasing blood pressure, which actually may be protecting the brain from ischemic effects of TAO. The significant variables associated with postoperative ischemic changes are duration and number of times temporary clips used. ICG-VA during aneurysm surgery is a simple yet highly powerful instrument that can warn the surgeon of impending ischemia during TAO. Many a times the importance of assessing the vascular flow after removal of the temporary clips is overlooked and this study urges the neurosurgeons to assess the vascular territory of interest both before and after the application of temporary clips so that chances of ischemia can be minimized.