Protective effect of dexmedetomidine combined with remifentanil on perioperative brain tissue in patients with severe traumatic brain injury and its influence on serum inflammatory markers

Taotao Luo; Xuezhi Zhang; Yating Luo; Boqi He; Yongle Xie

doi:10.2298/VSP241231037L

Taotao Luo Gansu University of Chinese Medicine, 35Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu Province, China; Tianshui First People’s Hospital, Qinzhou District, Tianshui, Gansu Province, China Dingxi East Road, Chengguan District, Lanzhou, Gansu Province, 200031, China
Xuezhi Zhang Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu Province, China; Tianshui First People’s Hospital, Qinzhou District, Tianshui, Gansu Province, China
Yating Luo Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu Province, China; Tianshui First People’s Hospital, Qinzhou District, Tianshui, Gansu Province, China
Boqi He Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu Province, China; Tianshui First People’s Hospital, Qinzhou District, Tianshui, Gansu Province, China
Yongle Xie Gansu University of Chinese Medicine, Chengguan District, Lanzhou, Gansu Province, China; Tianshui First People’s Hospital, Qinzhou District, Tianshui, Gansu Province, China

DOI: https://doi.org/10.2298/VSP241231037L

Keywords: analgesia;, brain;, craniocerebral trauma;, deep sedation;, dexmedetomidine;, quality of life;, remifentanil;, treatment outcome

Abstract

Background/Aim. Patients with a severe traumatic brain injury (TBI) demand intensive monitoring and treatment due to significant brain trauma or other accompanying causes, such as comorbidities or polytrauma. Patients with such injuries are under intense stress, leading to increased sympathetic excitability, and often experience agitation and pain. Appropriate sedation and analgesia are crucial for these patients, as they can reduce complications, mortality, and sequelae and improve quality of life. The aim of this study was to examine the impact of dexmedetomidine combined with remifentanil on postoperative sedation, analgesia, and cerebral oxygen metabolism in patients with TBI. Methods. A prospective, single-blind, randomized, controlled clinical study included 80 patients divided into two groups: a control group (CG) that received dexmedetomidine (n = 40) and an observation group (OG) that received dexmedetomidine combined with remifentanil (n = 40). Results. Compared to CG, OG demonstrated superior sedation and analgesia, reduced sedation and mechanical ventilation durations, and lower heart rate, mean arterial pressure, and respiratory rate. Additionally, OG showed statistically greater reductions in inflammatory markers and serum cortisol levels and higher β-endorphin levels. Cerebral oxygen metabolism indices also improved more in the OG postoperatively, although the differences were not statistically significant. Conclusion. Sedation and pain management strategy using of dexmedetomidine combined with remifentanil improved patient outcomes by speeding recovery and reducing physiological stress. Additional research is needed to determine the long-term effects of this combination on brain oxygen metabolism.

References

Wang H, He Y, Liang R, Wu X, Zhao L, Yang J, et al. A meta-analysis and systematic review of intracranial pressure moni-toring on severe craniocerebral injury. Ann Palliat Med 2021; 10(5): 5380−90.

Tian J, Zhang C, Wang Q. Analysis of craniocerebral injury in facial collision accidents. PLoS One 2020; 15(10): e0240359.

Gholami B, Haddad WM, Tannenbaum AR. Agitation and pain assessment using digital imaging. Annu Int Conf IEEE Eng Med Biol Soc 2009; 2009: 2176−9.

Oddo M, Crippa IA, Mehta S, Menon D, Payen JF, Taccone FS, et al. Optimizing sedation in patients with acute brain injury. Crit Care 2016; 20(1): 128.

Huang Q, Xu H, Xiao QS. Clinical research of different analge-sia methods on perianesthetic pain of patients with moderate and severe craniocerebral injury who have emergency opera-tion. Eur Rev Med Pharmacol Sci 2017; 21(3 Suppl): 88−92.

Roberts I, Shakur-Still H, Aeron-Thomas A, Beaumont D, Belli A, Brenner A, et al. Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 interna-tional RCT. Health Technol Assess 2021; 25(26): 1−76.

Af Geijerstam JL, Britton M. Mild head injury - mortality and complication rate: meta-analysis of findings in a systematic lit-erature review. Acta Neurochir (Wien) 2003; 145(10): 843−50.

Jha RM, Kochanek PM, Simard JM. Pathophysiology and treat-ment of cerebral edema in traumatic brain injury. Neurophar-macology 2019; 145(Pt B): 230−46.

Liu S, McLeod SL, Atzema CL, Austin PC, de Wit K, Sharma S, et al. Delayed intracranial hemorrhage after head injury among elderly patients on anticoagulation seen in the emergency de-partment. CJEM 2022; 24(8): 853−61.

Pittella JE, da Silva Gusmão SN. Intracerebral hemorrhage due to cerebral amyloid angiopathy after head injury: Report of a case and review of the literature. Neuropathology 2016; 36(6): 566−72.

Tasker RC. Analgesia, Sedation, and Intracranial Pressure: Questioning Our Approach in Pediatric Traumatic Brain Inju-ry. Crit Care Med 2016; 44(4): 851−2.

Bao ST, Wang SM, Lin MS. Clinical diagnosis and treatment of abdominal visceral injury complicated by craniocerebral injury. Chin J Traumatol 2006; 9(2): 105−7.

Ben Abdeljelil A, Freire GC, Yanchar N, Turgeon AF, Beno S, Bé-rubé M, et al. Pediatric Moderate and Severe Traumatic Brain Injury: A Systematic Review of Clinical Practice Guideline Recommendations. J Neurotrauma 2023; 40(21−2): 2270−81.

Pu B, Xue Y, Wang Q, Hua C, Li X. Dextromethorphan pro-vides neuroprotection via anti-inflammatory and anti-excitotoxicity effects in the cortex following traumatic brain injury. Mol Med Rep 2015; 12(3): 3704−10.

Shear DA, Williams AJ, Sharrow K, Lu XC, Tortella FC. Neu-roprotective profile of dextromethorphan in an experimental model of penetrating ballistic-like brain injury. Pharmacol Bi-ochem Behav 2009; 94(1): 56−62.

Hanzlick R. National Association of Medical Examiners Pedi-atric Toxicology (PedTox) Registry Report 3. Case submission summary and data for acetaminophen, benzene, carboxyhe-moglobin, dextromethorphan, ethanol, phenobarbital, and pseudoephedrine. Am J Forensic Med Pathol 1995; 16(4): 270−7.

Bushuven S, Kreuer S, Kranke P. Remifentanil Up2date - Part 1. Anasthesiol Intensivmed Notfallmed Schmerzther 2017; 52(7−08): 543−53. (German)

Stein D, Broderick M. Management of Head Trauma. Surg Clin North Am 2024; 104(2): 325−41.

Derakhshan A, Firoozi J, Esmaeili S, Bakhtiari E, Abbaspour M, Abrishami M, et al. Systemic prednisolone versus topical tranexamic acid for prevention of rebleeding in patients with traumatic hyphema: A randomized clinical trial. J Fr Oph-talmol 2022; 45(1): 9−12.

Tadevosyan A, Kornbluth J. Brain Herniation and Intracranial Hypertension. Neurol Clin 2021; 39(2): 293−318.

Stocchetti N, Carbonara M, Citerio G, Ercole A, Skrifvars MB, Smielewski P, et al. Severe traumatic brain injury: targeted management in the intensive care unit. Lancet Neurol 2017; 16(6): 452−64.

Visser K, Koggel M, Blaauw J, van der Horn HJ, Jacobs B, van der Naalt J. Blood-based biomarkers of inflammation in mild traumatic brain injury: A systematic review. Neurosci Biobe-hav Rev 2022; 132: 154−68.

Lin Y, Zhang J, Lu D, Zhang Y, Xu J, Wang S, et al. Uqcr11 al-leviates oxidative stress and apoptosis after traumatic brain in-jury. Exp Neurol 2023; 370: 114582.

Sarkar C, Jones JW, Hegdekar N, Thayer JA, Kumar A, Faden AI, et al. PLA2G4A/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegenera-tion after brain trauma. Autophagy 2020; 16(3): 466−85.

Zhang W, Qin Z, Xian K, Tang S. Assessment of plasma homo-cysteine levels in patients with craniocerebral injury and prog-nosis. J Int Med Res 2020; 48(3): 300060519882202.

Fu Y, Jin Z. Effects of Dexmedetomidine on Cognitive Func-tion, Oxidative Stress and Brain Protection in Patients Un-dergoing Craniocerebral Surgery. Actas Esp Psiquiatr 2024; 52(1): 19−27.

Yang ZH, Yin XJ, Fu GY. The correlation between CT find-ings of diffuse axonal injury and the expression of neuronal aquaporin in patients with craniocerebral injury. Eur Rev Med Pharmacol Sci 2022; 26(18): 6871−8.

Kenneally A, Cummins M, Bailey A, Yackey K, Jones L, Carter C, et al. Intranasal Dexmedetomidine Use in Pediatric Patients for Anxiolysis in the Emergency Department. Pediatr Emerg Care 2023; 39(9): 685−91.

Yu X, Franks NP, Wisden W. Sleep and Sedative States In-duced by Targeting the Histamine and Noradrenergic Systems. Front Neural Circuits 2018; 12: 4.

Aminnejad R, Hormati A, Shafiee H, Alemi F, Hormati M, Saeidi M, et al. Comparing the Efficacy and Safety of Dexme-detomidine/Ketamine with Propofol/Fentanyl for Sedation in Colonoscopy Patients: A Double blinded Randomized Clin-ical Trial. CNS Neurol Disord Drug Targets 2022; 21(8): 724−31.

Sridharan K, Sivaramakrishnan G. Comparison of Fentanyl, Remifentanil, Sufentanil and Alfentanil in Combination with Propofol for General Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Curr Clin Pharmacol 2019; 14(2): 116−24.

Patel MB, McKenna JW, Alvarez JM, Sugiura A, Jenkins JM, Guillamondegui OD, et al. Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using pro-pranolol and clonidine (DASH After TBI Study): study proto-col for a randomized controlled trial. Trials 2012; 13: 177.

Ahrens T, Frankhauser P, Lederbogen F, Deuschle M. Effect of single-dose sertraline on the hypothalamus-pituitary-adrenal system, autonomic nervous system, and platelet function. J Clin Psychopharmacol 2007; 27(6): 602−6.

Simon DW, McGeachy MJ, Bayır H, Clark RS, Loane DJ, Kochanek PM. The far-reaching scope of neuroinflammation af-ter traumatic brain injury. Nat Rev Neurol 2017; 13(3): 171–91. Erratum in: Nat Rev Neurol 2017; 13(9): 572.

Bilotta F, Gelb AW, Stazi E, Titi L, Paoloni FP, Rosa G. Phar-macological perioperative brain neuroprotection: a qualitative review of randomized clinical trials. Br J Anaesth 2013; 110 Suppl 1: i113–20.

Robertson CS, Gopinath SP, Goodman JC, Contant CF, Valadka AB, Narayan RK. SjvO2 monitoring in head-injured patients. J Neurotrauma 1995; 12(5): 891−6.

Liu M, Wang QQ, Lin WX, Ma BX, Lin QY. Effects of EEG burst suppression on cerebral oxygen metabolism and postop-erative cognitive function in elderly surgical patients: A ran-domized clinical trial. Medicine (Baltimore) 2023; 102(13): e33148.

Shadrin KV, Pakhomova VG, Kryukova OV, Rupenko AP, Yaro-slavtsev RN. Influence of oxygen uptake through the liver sur-face on the metabolism of ex vivo perfused liver during hy-poxia. Biochim Biophys Acta Gen Subj 2023; 1867(10): 130429.

Shademan B, Zakeri M, Abbasi S, Biray Avci C, Karamad V, Sogutlu F, Laghousi D, et al. Relationship between miRNA-21, miRNA-155, and miRNA-182 expression and inflammatory factors in cerebrospinal fluid from patients with multiple scle-rosis. Clin Neurol Neurosurg 2023; 232: 107873.

McPherson MJ, Hobson AD, Hernandez A Jr, Marvin CC, Waegell W, Goess C, et al. An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against im-mune-mediated inflammatory diseases. Sci Transl Med 2024; 16(739): eadd8936.

Shukla R, Kalita J, Haldar R, Misra UK. Blood-CSF-barrier permeability in tuberculous meningitis and its association with clinical, MRI and inflammatory cytokines. J Neuroimmunol 2022; 372: 577954.

Huang H, Fu G, Lu S, Chen S, Huo J, Ran Y, et al. Plasma pro-files of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study. Eur J Pediatr 2024; 183(8): 3359−68.