Non-traumatic subarachnoid haemorrhage (SAH) is a significant cause of death and disability globally, with an incidence of around 6 per 100,000 person-years. The initial treatment focuses on early aneurysm repair to prevent re-bleeding and reduce early brain injury risk. Management also addresses secondary brain injuries, including hydrocephalus, elevated intracranial pressure (ICP), delayed cerebral ischaemia (DCI), and other complications.
A critical factor in secondary brain injury is low brain tissue partial pressure of oxygen (PbtO2), which is linked to higher mortality and worse outcomes, even without elevated ICP. Decreased PbtO2 often results from reduced cerebral blood flow (CBF), systemic hypoxaemia, anaemia, microvascular dysfunction, or increased oxygen consumption in hypermetabolic states. Brain metabolic dysfunction, indicated by a high lactate to pyruvate ratio (LPR), also correlates with poor outcomes. Elevated LPR, whether due to ischaemia or mitochondrial dysfunction, can reflect metabolic distress. Despite improved CBF, metabolic dysfunction may persist, indicating that interventions focused on perfusion alone may not mitigate metabolic crises.
The TITAN study aimed to assess how low PbtO2 and metabolic dysfunction influence neurological outcomes and mortality in SAH patients. The study analysed SAH patients from five neurocritical care units who required invasive multimodal neuromonitoring. It visualised the relationship between episodes of low PbtO2 combined with elevated LPR and 6-month Glasgow Outcome Scale (GOS) scores using a colour-coded plot. A multivariate analysis was conducted to assess the association between the percentage of time spent with low PbtO2 and/or high LPR and neurological outcomes and mortality at 6 months.
The study included 232 SAH patients, with a median monitoring duration of 117 hours per patient. The colour-coded plot showed that combined episodes of low PbtO2 and elevated LPR were more common in patients with unfavourable neurological outcomes (GOS 1–3). This association was less clear in patients with isolated low PbtO2 or elevated LPR. In a multivariate model, the cumulative burden of low PbtO2 and elevated LPR was independently linked to unfavourable neurological outcomes.
The study found that combined episodes of low PbtO2 and high LPR were more common in patients with unfavourable neurological outcomes and non-survivors. The cumulative burden of low PbtO2 and energetic dysfunction was independently linked to an increased risk of long-term poor outcomes and mortality. Isolated low PbtO2 without concurrent metabolic dysfunction did not carry the same prognostic significance as episodes with a potential ischaemic profile (low PbtO2 and high LPR), which were associated with worse outcomes. High LPR with normal PbtO2 suggested mitochondrial dysfunction, even when cerebral perfusion appeared adequate.
The study emphasised the importance of a multimodal approach to neuromonitoring, where both PbtO2 and LPR are interpreted together. This could help avoid unnecessary interventions for isolated low PbtO2 values without metabolic evidence of ischaemia. The study also noted that ischaemic injury is a significant contributor to brain damage in SAH patients, leading to metabolic shifts and neuronal injury, with DCI being a major cause of long-term disability. The study found a high prevalence of DCI (50.4%), potentially due to the inclusion of severely ill patients.
Overall, study findings show that the combination of low PbtO2 and high LPR, indicating an ischaemic pattern, was linked to worse neurological outcomes at 6 months. Other pathological patterns, such as isolated low PbtO2 or high LPR without the ischaemic profile, had a less clear effect on patient outcomes.
Source: Intensive Care Medicine
Image Credit: iStock
References:
Gouvêa Bogossian E, Kempen B, Veldeman M, et al. Visualizing the burden of brain tissue hypoxia and metabolic dysfunction assessed by multimodal neuromonitoring in subarachnoid hemorrhage patients: the TITAN study. Intensive Care Med. 2025.
