Impact of Dexmedetomidine Versus Propofol on Intracranial Pressure in Adult Traumatic Brain Injury Patients: Randomized Controlled Double-Blind Trial

Overview

To investigate whether dexmedetomidine or propofol is more effective in controlling intracranial pressure (ICP) (assessed via optic nerve sheath diameter "ONSD" as a primary outcome) and which is more effective in suppressing lipid peroxidation (measured via malondialdehyde "MDA" as a secondary outcome). This double-blind randomized controlled trial aims to bridge this research gap by evaluating the biochemical neuroprotective efficacy alongside the clinical outcomes of both agents in TBI patients.

Traumatic brain injury (TBI) remains a leading cause of mortality and permanent disability worldwide, posing a major challenge in neurocritical care. The primary injury occurs at the moment of impact, resulting in immediate mechanical tissue disruption. However, the subsequent secondary brain injury develops over hours to days, driven by complex cascades of neuroinflammation, excitotoxicity, mitochondrial dysfunction, and severe oxidative stress (Werner and Engelhard, 2007). Oxidative stress is characterized by an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms. The brain is particularly vulnerable to oxidative damage due to its high oxygen consumption, high lipid content (especially polyunsaturated fatty acids), and relatively low levels of antioxidant enzymes (Hall et al., 2010). During secondary injury, massive ROS production leads to lipid peroxidation, a process that degrades cell membranes and disrupts cellular integrity. Malondialdehyde (MDA) is a well-established, highly stable end-product of lipid peroxidation. Elevated systemic and cerebrospinal fluid levels of MDA serve as a reliable and sensitive biomarker for quantifying the severity of oxidative stress and predicting neurological outcomes in TBI patients (Lorente et al., 2015). Sedation is a cornerstone in the management of mechanically ventilated TBI patients in the Intensive Care Unit (ICU). It is essential to decrease metabolic demands, facilitate mechanical ventilation, prevent spikes in intracranial pressure (ICP), and control agitation (Roberts et al., 2011). Dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, has emerged as a promising alternative in neurointensive care. It provides "conscious sedation" without causing significant respiratory depression, allowing for easier neurological evaluation. Beyond its sedative properties, evolving preclinical and clinical evidence suggests that dexmedetomidine exerts potent neuroprotective effects (Arain and Ebert, 2002). These effects are hypothesized to be mediated through the reduction of central sympathetic outflow, attenuation of neuroinflammation, and direct modulation of oxidative stress pathways, leading to a reduction in lipid peroxidation biomarkers like MDA (Wang et al., 2019). Propofol is a lipid-soluble anesthetic, used intravenously in the clinics for sedation in the ICU and for general anesthesia. The antioxidant properties of propofol have been attributed to the similarity of its chemical structure to known antioxidants such as butylhydroxytoluene and α-tocopherol. It has been reported that the antioxidant properties of propofol are not only inhibiting lipid peroxidation, but also scavenging the ROS that have been formed (Demiryürek et al., 1998).