Author: Shuo Wang, et al.
Journal of Neurosurgical Anesthesiology. 2026;38(2):115–123.
The choice between volatile anesthesia and total intravenous anesthesia may influence neurologic outcomes after aneurysmal subarachnoid hemorrhage. This systematic review and meta-analysis found that observational studies favored volatile anesthesia for reducing cerebral vasospasm and delayed cerebral ischemia, but randomized trials did not confirm these benefits.
Study Design
The investigators reviewed nine studies involving 1,459 adults undergoing surgical clipping or endovascular coiling for aneurysmal subarachnoid hemorrhage.
The analysis included:
- Four randomized controlled trials
- Five cohort studies
- Volatile anesthetics including isoflurane, sevoflurane, and desflurane
- Propofol-based total intravenous anesthesia
Because randomized and observational studies have different risks of bias, the investigators analyzed them separately.
The primary outcome was postoperative cerebral vasospasm. Secondary outcomes included delayed cerebral ischemia, cerebral infarction, and intraoperative brain swelling.
Cerebral Vasospasm
The five cohort studies suggested that volatile-based anesthesia was associated with a significantly lower risk of postoperative cerebral vasospasm.
Compared with total intravenous anesthesia, volatile anesthesia was associated with an approximately 28% relative risk reduction in vasospasm.
However, the randomized controlled trials found no significant difference between volatile anesthesia and total intravenous anesthesia. The confidence interval was wide, reflecting the small number of patients and events.
Therefore, the apparent benefit observed in cohort studies may represent a true neuroprotective effect, residual confounding, or differences in patient selection and perioperative management.
Delayed Cerebral Ischemia
Three cohort studies evaluated delayed cerebral ischemia.
Volatile-based anesthesia was associated with an approximately 37% relative reduction in delayed cerebral ischemia compared with total intravenous anesthesia.
This finding was statistically significant and consistent across the observational studies. However, randomized trial evidence was not available to confirm that volatile anesthesia caused the reduction.
Cerebral Infarction
Two randomized controlled trials evaluated postoperative cerebral infarction and found no significant difference between anesthetic techniques.
One cohort study also found no statistically significant difference in cerebral infarction between volatile anesthesia and total intravenous anesthesia.
Intraoperative Brain Swelling
Four randomized trials compared intraoperative brain swelling.
There was no significant difference between volatile anesthesia and propofol-based total intravenous anesthesia.
This is clinically important because volatile anesthetics can increase cerebral blood flow and cerebral blood volume. Despite these physiologic effects, the pooled randomized evidence did not demonstrate an increased risk of brain swelling during aneurysm surgery.
Possible Neuroprotective Mechanisms
Animal studies suggest that volatile anesthetics may reduce cerebral vasospasm, microvascular thrombosis, inflammation, and neuronal apoptosis after subarachnoid hemorrhage.
Proposed mechanisms include:
- Increased endothelial nitric oxide synthase activity
- Reduced inducible nitric oxide synthase activity
- Upregulation of hypoxia-inducible factor 1-alpha
- Reduced inflammatory signaling
- Improved cerebral microcirculation
Propofol has not demonstrated the same degree of protection against vasospasm in experimental subarachnoid hemorrhage models.
These biological mechanisms support the possibility that volatile anesthetics may provide neuroprotection, but clinical causation remains unproven.
Clinical Implications
The available evidence does not establish that volatile anesthesia is superior to total intravenous anesthesia for aneurysmal subarachnoid hemorrhage procedures.
Volatile anesthesia may be reasonable when reducing vasospasm or delayed cerebral ischemia is a priority. However, propofol-based total intravenous anesthesia may remain preferable when:
- Intracranial pressure is elevated
- Motor-evoked potential monitoring is required
- Reducing cerebral blood flow or brain volume is important
- Rapid adjustment of anesthetic depth is desired
Anesthetic selection should therefore be individualized rather than based solely on the observational association between volatile anesthesia and reduced vasospasm.
Limitations
The randomized trials were small, and only two reported the primary vasospasm outcome. All randomized trials were conducted in India, limiting geographic generalizability.
Three cohort studies were conducted by the same research group and may have included overlapping patient populations. Although sensitivity analysis excluding one potentially overlapping study produced similar findings, duplication remains a concern.
Definitions of cerebral vasospasm also varied among studies and included angiographic, symptomatic, and transcranial Doppler criteria.
Conclusion
Cohort studies suggest that volatile-based anesthesia may reduce postoperative cerebral vasospasm and delayed cerebral ischemia compared with propofol-based total intravenous anesthesia in patients undergoing aneurysm clipping or coiling.
Randomized controlled trials, however, found no significant differences in cerebral vasospasm, cerebral infarction, or intraoperative brain swelling.
The evidence is therefore promising but inconclusive. Larger, multicenter randomized trials are needed before volatile anesthesia can be recommended specifically to improve neurologic outcomes after aneurysmal subarachnoid hemorrhage.
We thank the Journal of Neurosurgical Anesthesiology for allowing us to summarize this important clinical research.