Elevated catecholamine levels following aneurysmal subarachnoid hemorrhage are associated with increased sympathetic nervous system activity, poorer outcomes, and higher mortality rates, according to a narrative review.
Researchers conducted a targeted literature search of PubMed, Scopus, Cochrane Library, Medline, Embase, and CINAHL through July 2024 to examine the relationship between catecholamines—including epinephrine, norepinephrine, and dopamine—and patient outcomes. Following aneurysm rupture, a surge in catecholamines occurs due to activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, increasing blood pressure and heart rate and potentially exacerbating the initial brain injury.
Elevated catecholamine levels contribute to secondary brain injury. Vasospasm typically develops between 4 and 14 days after hemorrhage and is associated with delayed cerebral ischemia, which occurs in up to 66% of patients. Catecholamine excess may also increase blood-brain barrier permeability through endothelial injury, oxidative stress, and inflammatory cytokine release, contributing to cerebral edema and increased intracranial pressure. In addition, oxidative stress, mitochondrial dysfunction, and excitotoxicity may contribute to neuronal injury and cell death.
The review also describes systemic complications associated with catecholamine excess. Cardiac dysfunction is common, with up to 28% of patients showing regional wall motion abnormalities and up to 15% developing global left ventricular dysfunction. Arrhythmias occur in 50% to 100% of patients and are associated with increased morbidity and mortality. Catecholamine excess has also been linked to neurogenic pulmonary edema and acute kidney injury through vasoconstriction and reduced organ perfusion. Metabolic effects include hyperglycemia, insulin resistance, and electrolyte imbalances, which are associated with worse outcomes.
Higher catecholamine concentrations are associated with poorer outcomes and increased mortality. Plasma catecholamine levels were higher in patients with unfavorable outcomes, suggesting a potential role as biomarkers for risk stratification.
Therapeutic approaches discussed in the review include beta-blockers and alpha-adrenergic antagonists, which have been explored as strategies to mitigate the effects of catecholamine surge, although further clinical study is needed. Calcium channel blockers such as nimodipine are used to prevent delayed cerebral ischemia, and exogenous catecholamines may be required to maintain adequate blood pressure and cerebral perfusion. Combination strategies, including milrinone with norepinephrine, have been associated with improved cerebral perfusion during secondary cerebral ischemia.
“[S]urge can lead to hemodynamic instability, cardiac dysfunction, cerebral vasospasm, and altered metabolism, and can influence overall systemic inflammatory responses thus influencing the overall outcomes in patients with aneurysmal [subarachnoid hemorrhages],” wrote lead author Samantha Nalliah of the School of Medicine at the University of Galway, and colleagues.
The researchers reported no conflicts of interest.
Source: Acute and Critical Care