Synergistic effects of neuroendoscopic minimally invasive surgery with mannitol and furosemide in managing hypertensive intracerebral hemorrhage

1. Introduction

Hypertensive intracerebral hemorrhage (HICH), a severe complication of hypertension, results from the dysfunction of small cerebral arteries and predominantly affects middle-aged and elderly individuals, posing significant risks to their health and survival [1]. This condition often occurs due to sudden increases in blood pressure triggered by activities such as strenuous exercise, exhaustion, or emotional stress in hypertensive patients. These surges can result in local brain damage, rupture of cerebral vessels, elevated intracranial pressure, and compromised cerebral blood flow, leading to severe consequences like paralysis, aphasia, and central nervous system failure [2, 3]. With its high mortality rate and rapid progression, HICH presents considerable challenges in treatment [4]. Pharmacotherapy in clinical practice aims to reduce intracranial pressure and alleviate edema [5]. However, the efficacy of drugs varies significantly among different agents. Mannitol, known for its potent diuretic effect, can help alleviate intracranial hypertension [6], while furosemide is used to manage brain edema. Conventional drugs primarily target intracranial pressure and hypertension control but may not adequately address symptoms such as elevated intracranial pressure, mass effect, and herniation following hematoma formation. In contrast, surgical intervention, particularly hematoma evacuation under direct visualization, can substantially decrease intracranial pressure and reduce the risk associated with toxic byproducts of hematomas, thus preserving brain tissue [7]. Surgical techniques for hematoma removal range from traditional craniotomy, which is invasive and associated with significant tissue damage and lengthy recovery, to neuroendoscopic minimally invasive surgery, which is characterized by reduced trauma, enhanced safety, and more favorable outcomes [8]. However, research on the integration of surgical and pharmacological treatments for HICH is limited. Therefore, this study retrospectively analyzes clinical data from 200 patients treated for hypertensive cerebral hemorrhage at our institution between July 2020 and July 2022 to investigate the combined impact of neuroendoscopic minimally invasive surgery with mannitol and furosemide therapy on this life-threatening condition.

2. Materials and methods

3. Results

4. Discussion

HICH represents a significant clinical emergency characterized by high mortality and morbidity. This condition often leads to complications, including cerebral ischemia, brain edema and neuronal death [9]. It predominantly affects middle-aged and elderly males. The pathophysiology of HICH involves sustained hypertension causing microscopic arterial changes, resulting in weakened vessel walls that are prone to necrosis and rupture upon acute pressure surges from factors such as emotional stress, overwork or intense mental effort [10]. The occurrence of a hemorrhage exacerbates intracranial pressure, impairs cerebral circulation, and induces neurological dysfunction, typically presenting with vomiting, nausea, dizziness, headache, coma and hemiplegia [11]. Brain edema is particularly detrimental, significantly influencing patient prognosis by compounding secondary damage post-HICH [12]. Addressing cerebral edema and reducing intracranial pressure are crucial for effective HICH management, aiding neural recovery, decreasing complication rates, and enhancing overall outcomes [13].

Surgical intervention is widely employed in clinical practice to evacuate hematomas, alleviate mass effect, and prevent secondary injury from toxic hematoma byproducts [14, 15]. Neuroendoscopic minimally invasive surgery has gained popularity due to its reduced invasiveness and lower complication rates, emerging as a prominent treatment modality. However, postoperative management plays a crucial role in avoiding adverse outcomes, underscoring the importance of selecting appropriate osmotherapy agents [16]. Mannitol, an osmotic diuretic, rapidly elevates plasma osmolality, drawing interstitial fluid into the vascular compartment, thereby promoting dehydration and potentially improving cerebral perfusion. Furosemide, a loop diuretic, inhibits sodium and water reabsorption in the renal tubules, thus controlling cerebral edema [17]. Our study findings demonstrate that the experimental group experienced a reduction in both edema extent and hematoma volume compared to the control group, suggesting that a combination of minimally invasive surgery with mannitol and furosemide can effectively reduce edema and hematoma size.

Mannitol’s efficacy as an edema treatment stems from its ability to increase plasma osmotic pressure without undergoing metabolism in the body, facilitating efficient extracellular and cerebrospinal fluid excretion, thereby alleviating edema symptoms [18]. Additionally, it exhibits diuretic properties, enhancing blood volume, glomerular filtration rate, and prostaglandin production, collectively expediting fluid excretion and reducing intracranial pressure [19]. Furosemide functions by inhibiting the uptake of sodium, potassium, and chloride ions, leading to diuresis and amelioration of cerebral edema, in addition to reducing cerebrospinal fluid production and, consequently, intracranial pressure [20]. Ultimately, our research confirms that integrating surgical procedures with pharmacological therapy significantly reduces postoperative hematoma and edema. The results indicate that the experimental group demonstrates a higher total efficacy rate and markedly reduced NIHSS scores after 7 days of treatment compared to controls. This underscores the effectiveness of neuroendoscopic surgery coupled with mannitol and furosemide in HICH treatment, leading to improved clinical outcomes. Neuroendoscopic surgery benefits from enhanced visualization of the operative field through direct lighting and precise ultrasound-guided hematoma localization, ensuring efficient removal and better clearance rates [21]. Additionally, mannitol, an established osmotic diuretic, draws water from edematous brain tissue into the vascular system for renal excretion. This action effectively reduces intracranial pressure, mitigates cerebral edema, and prevents secondary damage following HICH. Consequently, the synergistic effect of combining surgical intervention with mannitol administration appears to enhance patient outcomes.

After treatment, the levels of LPO, NSE and S-100β in the experimental group were found to be significantly lower than those in the control group, indicating that the dual treatment modality effectively mitigates damage to the intracranial nervous system. NSE and S-100β proteins serve as established indicators of neuronal injury; NSE is a cytoplasmic glycolytic enzyme released by damaged neuroendocrine cells, while S-100β is a glial-derived calcium-binding protein. Under physiological conditions, these proteins are present at low concentrations within cells, but their levels surge in response to neuronal injury [22]. LPO plays a crucial role in regulating the equilibrium between oxygen-free radical activity and lipid peroxidation processes. Disruption of this balance, as seen during inflammatory responses, leads to elevated LPO, triggering a cascade of oxidative stress that impairs neural structures and tissues. Brain edema is a key factor in the secondary damage caused by HICH. In clinical settings, mannitol serves as a frontline diuretic post-surgery to promote dehydration and alleviate brain swelling, thus reducing intracranial pressure and enhancing plasma osmolarity. It is metabolized via the kidneys, facilitating the clearance of waste substances. Furosemide, on the other hand, inhibits sodium uptake into compromised brain tissue, diminishes cerebrospinal fluid production, and through its diuretic effect, concentrates blood proteins, acting as an osmotic dehydrating agent. The combination use of mannitol and furosemide not only better regulates serum biomarker levels but also aids in reducing intracranial pressure, averting various postoperative complications, and bolstering neurological function. After treatment, the Q and V values in the experimental group were significantly higher than those in the control group, while the R value was notably lower than in the control group. These findings suggest that adjuvant therapy with mannitol and furosemide enhances cerebral circulation in patients. Furosemide contributes to this improvement by inhibiting the breakdown of prostaglandins, elevating levels of prostaglandin E2, inducing vasodilation, and specifically augmenting renal blood flow, leading to lowered renal vascular resistance and heightened perfusion in the kidney’s deep cortex. This effect facilitates more rapid elimination of toxins and supports systemic recovery. Accordingly, integrating surgical intervention with pharmacotherapy appears to optimize cerebral hemodynamic parameters. However, the limited sample size of this study may introduce biases in the outcomes. Future research with expanded sample sizes and multicenter contributions could enhance result validity.

5. Conclusions

In conclusion, the combination of neuroendoscopic minimally invasive surgery with mannitol and furosemide therapy demonstrated promising benefits in managing HICH by effectively enhancing neurological function, reducing NIHSS scores and promoting cerebral blood flow, thereby warranting broader clinical application.

Availability of data and materials

The authors declare that all data supporting the findings of this study are available within the paper and any raw data can be obtained from the corresponding author upon request.

Author contributions

HX and JTD—designed the study and carried them out. HX, JTD, GGW, SLW, HHD and YJH—supervised the data collection. HX, JTD, GGW, SLW and HHD—analyzed the data. HX, JTD, GGW and SLW—interpreted the data, prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

Ethics approval and consent to participate

Ethical approval was obtained from the Science and Technology Ethics Committee of the First Affiliated Hospital of Shihezi University (Approval no. KJX2022-084-01). Written informed consent was obtained from a legally authorized representative for anonymized patient information to be published in this article.

Acknowledgment

Not applicable.

Funding

This work was supported by Scientific Research Fund of Shihezi University; Research Project of the First Affiliated Hospital of Shihezi University (Grant No. ZZZC202180 and ZD202010).

Conflict of interest

The authors declare no conflict of interest.