To our knowledge, this is the first systematic review and meta-analysis focused exclusively on surgically clipped cerebral aneurysms evaluating the impact of intraoperative rupture (IOR) on neurological outcomes. Across 19 studies involving 925 patients, IOR was associated with increased risks of poor functional outcome (RR 1.67) and mortality (RR 2.11), with even higher risks when rupture occurred in the setting of SAH [1,2,3,4].

The approximately one-third rate of poor outcomes among patients experiencing IOR highlights the substantial physiological disruption caused by rupture. IOR may occur before or during aneurysm neck dissection, often resulting in abrupt loss of operative control, impaired visualization, and an increased risk of ischemic injury or direct vessel damage.

When a rupture occurs prior to the establishment of proximal and distal control, the hemorrhage could continue for a relatively long period of time, leading to increased intracranial pressure and subsequent cerebral swelling, which may lead to further neurological injury [6, 9, 12]. Such rupture prior to any apparent aneurysm manipulation is much more common with previously ruptured aneurysms, which is inherently fraught with complications. Surgical maneuvers such as brain retraction or parent vessel manipulation may precipitate such rupture, resulting in prolonged hemorrhage, cerebral swelling, and ischemic injury.

Pooled analyses suggested a trend toward higher poor-outcome rates with increasing aneurysm size; however, limited data in larger size strata preclude firm conclusions. Similarly, MCA and ACoA aneurysms showed slightly higher pooled proportions of poor outcomes than other locations, but these represent associations rather than definitive causal effects. These trends may reflect differences in anatomical accessibility, surgical exposure, and timing of proximal control, though independent effects of location cannot be determined [10, 11].

Era-based analyses suggested attenuation of risk in contemporary series, consistent with advances in surgical exposure, temporary clipping, and anesthetic management [9, 14, 16]; however, IOR remained significantly associated with poor outcomes. Sensitivity analyses using alternative effect measures and continuity corrections confirmed the robustness of these associations.

The high heterogeneity across studies likely reflects variability in patient characteristics, aneurysm morphology, surgeon experience, and institutional protocols [1, 9, 13]. Multivariate analyses identified aneurysm complexity, morphology, and poor preoperative clinical grade as predictors of poor outcome after IOR, underscoring the multifactorial nature of risk [12, 15, 16]. These findings highlight the importance of integrating patient-, aneurysm-, and procedure-level factors into preoperative risk assessment and intraoperative decision-making [36,37,38].

While refinements in microsurgical techniques, anesthetic management, and temporary clipping strategies have reduced the frequency and severity of IOR over the past decades [6, 7, 12, 14], its association with adverse outcomes persists, indicating that these advances have mitigated but not eliminated the clinical consequences of rupture.

Therefore, the primary strategy for managing IOR is to make every effort to prevent it, as our results demonstrate that IOR can negatively impact patient outcomes, particularly in patients with SAH. Proper patient positioning, gravity-assisted retraction, and meticulous subarachnoid dissection to achieve a relaxed brain are essential, and forceful retraction should be avoided. Adequate proximal control via subarachnoid dissection facilitates safe temporary clip placement and may require skull base drilling or cervical ICA exposure. Testing of the feasibility of the proximal temporary clip placement before proceeding to the dissection of the aneurysm is of paramount importance. Following the proximal and distal control of the peri-aneurysmal vessels, the aneurysm neck should be dissected. Dissection of the aneurysm dome should be postponed to the very last moments of aneurysm preparation. A large, tense aneurysm may require complete trapping to make it softer and more easily clippable. The suction decompression technique for certain ICA aneurysms is a useful way to facilitate aneurysm dissection and clipping [39]. The surgeon must determine the optimal timing for temporary clipping, ensuring it is neither too early, which could lead to excessive ischemia, nor too late, as the fragile aneurysm wall may rupture before the parent vessel(s) are temporarily clipped. A tear in the neck of the aneurysm is a dreaded complication that may be difficult to manage [40, 41].

Unfortunately, despite taking all necessary precautions, an IOR may still occur. All the maneuvers mentioned above are part of a contingency plan in case of an IOR. Therefore, it is essential to anticipate this possibility and ensure that everything is properly prepared to manage it effectively. Additional measures may be taken to further facilitate the management of an IOR should it happen. A large craniotomy in cases of a previously ruptured aneurysm helps mitigate the impact of brain swelling in case of an IOR. Having an external ventricular drain to control the rapid rise of the intracranial pressure (or at least having prepared the cranial area for a ventriculostomy beforehand), coordination with anesthesia and neuromonitoring teams for optimizing blood pressure and pharmacologic neuroprotection, as well as preparation for administration of adenosine to temporarily pause the hemorrhage while a temporary clip is being applied to the parent vessel increase the seamlessness of managing IOR. The surgeon should avoid the temptation to blindly tamponade the bleeding area and instead try to use a combination of suction and tamponade of the bleeding to locate the proximal parent vessel to apply a temporary clip. With proper suctioning of the blood, the window opens for establishing proximal control and placing a temporary clip on the parent vessel. Having three suction tubes in the field helps to rapidly switch out any nonfunctioning suction tip. Cross-matched blood should be available in the room at the start of the case to prevent loss of control due to massive blood loss during the bleeding time.

Typically, the same strategies could be applied when the aneurysm ruptures during the dissection of its neck. However, in such a case, the proximal and distal vessel controls have already been established, and application of temporary clips to shut off the blood flow into the aneurysm should be facilitated. If brisk back-bleeding persists, a distal clip should be placed when necessary. It is reasonable to believe that an IOR, occurring before achieving both proximal and distal control, is more likely to lead to poor outcomes. Therefore, all efforts should be made to reduce the risk of an early IOR.

These findings underscore the importance of meticulous preoperative planning and intraoperative strategies, including assessment of aneurysm morphology, judicious temporary clipping, and rapid proximal control, to mitigate the consequences of rupture [6, 12, 15, 16, 27, 28, 42]. One could argue that a properly timed temporary clipping of the parent artery would provide a beneficial outcome, as post-rupture proximal and distal control may eventually lead to a longer ischemia time due to the compounded complexity of the situation. Awareness of potential associations with aneurysm size and location can guide intraoperative vigilance but should not be overinterpreted as definitive predictors of outcome. Patient counseling should incorporate the spectrum of potential outcomes following IOR, supporting informed decision-making and realistic expectations [1, 3, 29, 43].

Limitations of this meta-analysis include heterogeneity in the definition and timing of IOR, incomplete reporting of baseline clinical grades, and the predominance of retrospective single-center studies, which limit the generalizability of the findings. Additionally, few studies reported multivariate-adjusted effect estimates, leaving the possibility of residual confounding [1, 9, 13, 14]. Despite these constraints, sensitivity analyses demonstrated consistent directionality and magnitude of effect across study subgroups.

Future research should prioritize the development of standardized definitions for IOR and the systematic reporting of functional outcomes. Prospective, multicenter studies would improve generalizability and provide a stronger basis for risk modeling. Advanced intraoperative monitoring techniques such as indocyanine green angiography, neuromonitoring, and continuous hemodynamic assessment may help prevent or respond to rupture events more rapidly [44, 45]. Integrating patient-specific factors, aneurysm morphology, and surgeon experience into predictive models could inform individualized operative strategies [46, 47]. Collaborative registries that capture both intraoperative events and long-term functional outcomes would further strengthen evidence-based approaches to aneurysm surgery [48, 49].