Effect of early stepwise controlled decompression combined with mild hypothermia therapy on efficacy, cerebral edema volume, and serum biochemical indices in patients with severe hypertensive intracerebral hemorrhage

Abstract

Objective: To investigate the effects of early stepwise controlled decompression combined with mild hypothermia therapy (MHT) on clinical outcomes in patients with severe hypertensive intracerebral hemorrhage (sHICH). Methods: A total of 80 sHICH patients were included, with 32 cases in the control group receiving conventional craniotomy for hematoma evacuation and MHT, and 48 cases in the observation group undergoing early stepwise controlled decompression plus MHT. The two groups were compared in terms of treatment efficacy, hematoma clearance rate, prognosis, National Institutes of Health Stroke Scale (NIHSS) and Functional Ambulation Category (FAC) scores, complications, cerebral edema volume, and serum biochemical indices. Results: The observation group demonstrated significantly better efficacy, higher hematoma clearance rates, and improved clinical outcomes compared to the control group (all P<0.05). Postoperatively, the observation group had significantly lower NIHSS scores, reduced levels of neuron-specific enolase, central nervous system-specific protein, and malondialdehyde, as well as lower incidences of encephalocele, cerebral infarction, and delayed intracranial hematoma (all P<0.05). Additionally, cerebral edema volume was significantly reduced, while FAC scores were notably higher in the observation group (both P<0.05). Conclusion: Early stepwise controlled decompression combined with MHT is highly effective in the treatment of sHICH, leading to better neurological recovery, reduced cerebral edema, and improved biochemical profiles.

Introduction

Intracerebral hemorrhage (ICH) is a severe neurological condition primarily caused by the non-traumatic rupture of blood vessels within the brain parenchyma, posing a significant threat to human health [1]. Hypertension is a major risk factor, contributing to cerebral microvascular hyaline degeneration, fibrosis, and abnormal hemodynamic changes, which can lead to decreased vascular elasticity and the development of hypertensive intracerebral hemorrhage (HICH) [2-4]. Patients with HICH often present with headache, agitation, lethargy, coma, nausea, and vomiting. The resulting increase in intracranial pressure can exacerbate cerebral edema, cause neurological impairment, and, in severe cases, lead to disability or death [5,6].

Severe HICH (sHICH) is typically defined by a Glasgow Coma Scale score of <8, a hematoma volume >50 mL, or a midline shift >1 cm, indicating a more critical condition [7]. Given the current lack of an optimal treatment strategy for sHICH [8], further refinement and optimization of therapeutic approaches are urgently needed.

Surgical intervention remains the primary treatment for sHICH, aiming to rapidly evacuate the hematoma and restore neurological function [8]. Conventional craniotomy effectively removes the hematoma, alleviates mass effect, and achieves hemostasis [9]. However, this approach has notable limitations, including prolonged operative time, significant surgical trauma, high costs, and an elevated risk of postoperative complications [10,11]. In contrast, early stepwise controlled decompression is an optimized surgical technique that considers intracranial pressure dynamics and performs gradual decompression, thereby offering enhanced vascular protection [12]. This method not only reduces cerebral perfusion but also rapidly lowers intracranial pressure to facilitate hematoma evacuation [13].

Additionally, mild hypothermia therapy (MHT) is a minimally invasive neuroprotective strategy commonly employed in the management of acute brain injury-associated cerebral edema [14,15]. Studies suggest that the neuroprotective effects of MHT are mediated through its regulation of cerebral metabolism, promotion of lactate clearance, reduction of cerebral oxygen consumption, and maintenance of blood-brain barrier integrity [16].

This study aims to compare the clinical outcomes of early stepwise controlled decompression plus MHT versus conventional craniotomy plus MHT in patients with sHICH.

Materials and methods

Patient information

This retrospective study included 80 sHICH patients admitted to Tangshan Gongren Hospital between July 2020 and January 2024. Among them, 32 patients (control group) underwent conventional craniotomy for hematoma evacuation plus MHT, while 48 patients (observation group) received early stepwise controlled decompression plus MHT. The study protocol was approved by the Ethics Committee of Tangshan Gongren Hospital.

Inclusion and exclusion criteria

Inclusion criteria: Patients meeting the diagnostic criteria for HICH were included if they had supratentorial hemorrhage confirmed by cranial computed tomography (CT), a Glasgow Coma Scale score of ≤8, a history of hypertension, a hematoma volume of 30-50 mL, and complete clinical data.

Exclusion criteria: Patients were excluded if they had unstable vital signs, suspected cerebral aneurysm rupture or vascular malformations, traumatic hematoma, brainstem or cerebellar hemorrhage, coagulation disorders, significant dysfunction of the heart, lungs, or kidneys, or were on long-term anticoagulant therapy.

Methods

The control group underwent conventional craniotomy for hematoma evacuation combined with MHT. Preoperatively, the scalp was marked, and a skin-muscle flap was dissected layer by layer. Following skull drilling, the dura mater was suspended and incised, allowing access to the hematoma cavity by gently separating brain tissue along the lateral fissure. A conventional microscopic cortical fistulation was performed for hematoma evacuation, and meticulous hemostasis was ensured. The decision to retain or remove the bone flap depended on intracranial pressure status.

In the observation group, early stepwise controlled decompression combined with MHT was performed. The hematoma location and extent were determined via cranial CT, and the lateral fissure projection and hematoma center were marked. A frontotemporal bone flap craniotomy was performed, followed by rapid drilling. The dura mater was incised in a cross-like manner while avoiding superficial cerebral vessels. A drainage tube or puncture needle was inserted into the hematoma center to aspirate 5-10 mL of blood for controlled decompression, with adjustments made as necessary. After partial decompression, the bone window was enlarged, and the bone flap was milled. If intracranial pressure remained high, stepwise hematoma evacuation continued until decompression was adequate and encephalocele was absent. If intracranial pressure persisted at a high level after hematoma evacuation, a tension-reducing suture of the dura mater was performed, and the bone flap was removed for decompression. In cases with stable intracranial pressure, the dura mater was routinely sutured, and the bone flap was preserved.

Postoperatively, both groups received standard care, including infection control, dehydration therapy, acid-base balance maintenance, and correction of water-electrolyte disturbances. MHT was initiated using a water-circulating cooling blanket, reducing rectal temperature to 33-35°C within 4-6 hours. Patients were administered a continuous infusion of a muscle-lytic cocktail (200 mg of Tracrium [Shanghai Hengrui Pharmaceutical Co., Ltd., H20061298], 100 mg of Chlorpromazine [Shanxi Fenhe Pharmaceutical Co., Ltd., H14021851], and 20 mL of normal saline [Huaren Pharmaceutical Co., Ltd., H20034093]) at 2-4 mL/h for three days. Controlled rewarming followed, with the temperature gradually increased by 1°C every 4-6 hours over 12-24 hours until stabilizing at 36.5-37°C.

Outcome measures

Efficacy [17]. Treatment efficacy was evaluated based on the following criteria: Marked effectiveness: Significant alleviation of all clinical symptoms with >90% reduction in neurological deficits; Effectiveness: Improvement in clinical symptoms with a 75-90% reduction in neurological deficits; Ineffectiveness: Failure to meet the above criteria. The total effective rate was calculated as the sum of the marked effectiveness and effectiveness rates.

Hematoma clearance rate [18]. Hematoma clearance was assessed via CT reexamination two days postoperatively. The clearance rate/% = volume of cleared hematoma/volume of preoperative hematoma × 100%.

Prognosis [19]. Patients were followed up for six months postoperatively, and outcomes were assessed using the Glasgow Outcome Scale, which ranges from grade 1 to 5: Grade 1: Death; Grade 2: Vegetative state; Grade 3: Severe disability (conscious but dependent on daily care); Grade 4: Mild disability (capable of independent living and work with certain limitations); Grade 5: Good recovery (minor deficits but able to live and work normally).

Neurological function [20]. The National Institutes of Health Stroke Scale (NIHSS) was used to assess neurological function, with scores ranging from 0 to 42. Higher scores indicate greater neurological impairment.

Lower limb mobility [21]. The Functional Ambulation Category (FAC) was employed to evaluate lower limb function, where higher scores indicate better mobility.

Complication incidence [22]. The occurrence of adverse events, including encephalocele, cerebral infarction, delayed intracranial hematoma, arrhythmia, and chills, was recorded for both groups, and the incidence rate was calculated.

Cerebral edema volume [23]. Cranial CT scans were performed on postoperative days 7 and 14. The cerebral edema area in each layer was measured using an image analysis system, and the total cerebral edema volume was calculated by multiplying the edema area by the slice thickness.

Serum biochemical indices [24]. Fasting venous blood samples (5 mL) were collected from each patient before surgery and on postoperative day 7. After centrifugation, serum levels of neuron-specific enolase (NSE), central nervous system-specific protein S100-β, and malondialdehyde (MDA) were quantified using enzyme-linked immunosorbent assay.

Statistical analysis

Continuous variables were expressed as mean ± standard error of the mean (Mean ± SEM). Between-group comparisons were conducted using independent sample t-tests, while within-group comparisons utilized paired t-tests. Categorical data were reported as percentages and analyzed using the χ² test. All statistical analyses were performed using SPSS 20.0, with a significance level of P<0.05.

The sample size was determined using a validated sample-size calculation formula, accounting for a 10% dropout rate. The calculation indicated that a minimum of 37 participants per group (total n = 74) was required for adequate statistical power. The sample size included in this study fully met this requirement. The sample-size calculation formula is as follows:

$$\mathrm{n}=\frac{2\times {(Z_{\alpha /2}+Z_{\beta })}^2\times \left[p(1-p)\right]}{{\Delta }^2}$$

Results

Comparison of demographic characteristics

The comparison of demographic characteristics between the two groups showed no significant differences in sex, age, body mass index (BMI), time from onset to treatment or bleeding type (all P>0.05), indicating clinical comparability (Table 1).

Table 1.

Comparison of demographic characteristics

Indicators	Control group (n = 32)	Observation group (n = 48)	χ2/t	P
Gender			0.034	0.854
Male	18 (56.25)	28 (58.33)
Female	14 (43.75)	20 (41.67)
Age (years)	60.06±9.33	57.56±9.87	1.134	0.260
Body mass index (kg/cm2)	23.31±5.28	22.75±5.46	0.455	0.650
Duration of time from onset (h)	13.00±3.75	12.73±4.26	0.291	0.772
Bleeding type			0.543	0.762
Basal ganglia hemorrhage	14 (43.75)	25 (52.08)
Frontal lobe hemorrhage	12 (37.50)	15 (31.25)
Temporal lobe hemorrhage	6 (18.75)	8 (16.67)

Comparison of efficacy

The total effective rate in the observation group was 95.83%, significantly higher than the 71.88% observed in the control group (P<0.05) (Table 2).

Table 2.

Comparison of efficacy

Indicators	Control group (n = 32)	Observation group (n = 48)	χ2	P
Marked effectiveness	9 (28.13)	18 (37.50)
Effectiveness	14 (43.75)	28 (58.33)
Ineffectiveness	9 (28.13)	2 (4.17)
Total effectiveness	23 (71.88)	46 (95.83)	9.293	0.002

Comparison of hematoma clearance rates

Hematoma clearance rates were significantly better in the observation group (P<0.05). A higher number of patients achieved a clearance rate of 90-100% compared to the control group (P<0.05). In contrast, significantly fewer patients in the observation group had a clearance rate below 80% compared to the control group (P<0.05) (Table 3).

Table 3.

Comparison of hematoma clearance rates

Indicators	Control group (n = 32)	Observation group (n = 48)	χ2	P
90-100%	11 (34.38)	34 (70.83)	10.370	0.001
80-89%	13 (40.63)	11 (22.92)	2.867	0.090
<80%	8 (25.00)	3 (6.25)	5.692	0.017

Comparison of prognosis

Based on the Glasgow Outcome Scale at the six-month follow-up, the observation group had significantly fewer patients with a GOS range of 1-3 and more patients with a range of 4-5 than the control group (P<0.05) (Table 4).

Table 4.

Comparison of prognosis

Indicators	Control group (n = 32)	Observation group (n = 48)	χ2	P
Grade 1	5 (15.63)	1 (2.08)	5.075	0.024
Grade 2	6 (18.75)	2 (4.17)	4.537	0.033
Grade 3	14 (43.75)	6 (12.50)	10.000	0.002
Grade 4	6 (18.75)	29 (60.42)	13.545	<0.001
Grade 5	1 (3.13)	10 (20.83)	5.077	0.024

Comparison of NIHSS and FAC scores

Preoperative NIHSS and FAC scores were comparable between the two groups (both P>0.05). Postoperatively, both groups exhibited decreased NIHSS scores and increased FAC scores, with the observation group showing a significantly lower NIHSS score and a higher FAC score than the control group (both P<0.05) (Figure 1).

Figure 1.

Comparison of NIHSS and FAC scores. A. Comparison of NIHSS before and after surgery. B. Comparison of FAC before and after surgery. Note: *P<0.05, **P<0.01 vs. preoperative levels; #P<0.05 vs. control group. NIHSS, the National Institutes of Health Stroke Scale; FAC, Functional Ambulation Category.

Comparison of complication incidence

The incidence of complications, including encephalocele, cerebral infarction, delayed intracranial hematoma, arrhythmia, and chills, was analyzed. The observation group had significantly lower incidence rates of encephalocele, cerebral infarction, and delayed intracranial hematoma compared to the control group (all P<0.05). However, the incidence rates of arrhythmia and chills were similar between the two groups (both P>0.05) (Table 5).

Table 5.

Comparison of complications

Indicators	Control group (n = 32)	Observation group (n = 48)	χ2	P
Encephalocele	5 (15.63)	1 (2.08)	5.075	0.024
Cerebral infarction	5 (15.63)	1 (2.08)	5.075	0.024
Delayed intracranial hematoma	4 (12.50)	0 (0.00)	6.316	0.012
Arrhythmia	1 (3.13)	0 (0.00)	1.519	0.218
Chills	1 (3.13)	1 (2.08)	0.085	0.770

Comparison of cerebral edema volume

Cerebral edema volume was measured on postoperative days 7 and 14. The observation group had significantly lower cerebral edema volumes at both time points compared to the control group (both P<0.05) (Figure 2).

Figure 2.

Comparison of cerebral edema volume. Inter-group comparison of brain edema volume 7 days after surgery. Inter-group comparison of cerebral edema volume 14 days after surgery. Note: **P<0.01 vs. control group.

Comparison of serum biochemical indices

Preoperative levels of NSE, S100-β, and MDA were similar between the two groups (all P>0.05). Postoperatively, all three indices showed a greater reduction in the observation group compared to the control group (all P<0.05) (Figure 3).

Figure 3.

Comparison of serum biochemical indices. A. Comparison of NSE levels before and after surgery. B. Comparison of S100-β levels before and after surgery. C. Comparison of MDA levels before and after surgery. Note: *P<0.05, **P<0.01 vs. preoperative levels; #P<0.05 vs. control group. NSE, neuron-specific enolase; S100-β, central nervous system-specific protein; MDA, malondialdehyde.

Discussion

HICH is a common type of intracerebral hemorrhage associated with emotional agitation, excessive physical exertion, and cognitive overload [25]. Its occurrence leads to brain neuronal damage, while the hematoma compresses surrounding brain tissue, increasing the risk of secondary cerebral edema, elevated intracranial pressure, and potentially life-threatening brain herniation [26]. Consequently, HICH patients face a high risk of early mortality and, if they survive, may experience long-term sequelae such as dysphagia, cognitive impairment, and motor dysfunction [27]. Reducing postoperative complications, improving treatment efficacy, minimizing cerebral edema, and optimizing serum biochemical indices are key challenges in the management of sHICH.

Early stepwise controlled decompression enables the gradual regulation of intracranial pressure during surgery. When applied to sHICH patients, it allows for early rapid drilling, partial hematoma drainage, and progressive intracranial pressure control, thereby enhancing therapeutic outcomes while ensuring procedural safety [28]. In this study, the total effective rate in the observation group (95.83%) was significantly higher than that in the control group (71.88%), indicating that early stepwise controlled decompression combined with MHT offers greater clinical benefits compared to conventional craniotomy plus MHT.

Moreover, patients in the observation group exhibited higher hematoma clearance rates and better overall prognoses. Postoperatively, they demonstrated significantly lower NIHSS scores and higher FAC scores compared to the control group, suggesting superior neurological recovery and functional mobility. The improved outcomes may be attributed to the procedural strategy of early stepwise controlled decompression, which removes only 5-10 mL of hematoma per step. This approach not only minimizes disruption to normal brain tissue but also reduces the risk of brain tissue displacement caused by reperfusion injury [29]. Ling et al. [30] reported that early stepwise controlled decompression significantly improved neurological recovery and daily living abilities in patients with cerebral hemorrhage, aligning with our findings. In this study, complication analysis revealed that the observation group had a lower incidence of encephalocele, cerebral infarction, and delayed intracranial hematoma compared to the control group, suggesting that early stepwise controlled decompression combined with MHT can effectively reduce postoperative complications in patients with sHICH.

The analysis of cerebral edema showed that the observation group had significantly lower cerebral edema volumes on postoperative days 7 and 14 compared to the control group, indicating the efficacy of early stepwise controlled decompression plus MHT in reducing postoperative brain edema. This may be attributed to the gradual repositioning of brain tissue toward its original anatomical location during stepwise decompression, which helps prevent acute cerebral vascular congestion, perfusion pressure breakthrough, and mechanical injury. These mechanisms contribute to the protection of the blood-brain barrier, a reduction in acute brain swelling, and the mitigation of secondary neurological damage [31,32].

Furthermore, serum biochemical analysis demonstrated a significant postoperative reduction in NSE, S100-β, and MDA levels in the observation group, which were lower than those in the control group. This suggests that early stepwise controlled decompression plus MHT effectively reduces abnormally elevated levels of NSE, S100-β, and MDA - key biomarkers of brain injury. The downregulation of these markers reflects improved hematoma clearance, reduced intracranial pressure, decreased brain tissue damage, and alleviation of oxidative stress [33-35]. The neuroprotective effects observed in this study may be attributed to the controlled and orderly removal of hematoma at the lesion site, which optimizes intracranial pressure regulation and minimizes oxidative stress-induced injury [36,37].

This study highlights the comprehensive clinical benefits of early stepwise controlled decompression plus MHT in sHICH patients by evaluating multiple aspects, including efficacy, hematoma clearance, prognosis, neurological function, lower limb mobility, complication rates, cerebral edema volume, and serum biochemical indices. The findings confirm the superiority of this approach over conventional craniotomy plus MHT, providing valuable insights into optimal treatment strategies in sHICH patients. Implementing this approach in clinical practice may contribute to improved patient outcomes and a higher quality of care.

In conclusion, early stepwise controlled decompression combined with MHT significantly enhances treatment efficacy, improves functional mobility and prognosis, increases hematoma clearance, and alleviates neurological deficits. Additionally, it reduces brain edema volume and downregulates NSE, S100-β, and MDA levels, while also lowering the incidence of complications such as encephalocele, cerebral infarction, and delayed intracranial hematoma. These findings underscore its potential as an effective and safe therapeutic strategy for sHICH management.

This study also has several limitations, including its single-center, retrospective design, which may limit generalizability, and a relatively small sample size that could impact statistical robustness. The follow-up period was short, assessing prognosis only up to six months, and lacked advanced neuroimaging assessments such as MRI, which could provide deeper insights into brain recovery. Additionally, potential selection bias, limited biochemical markers, and variability in surgical execution may have influenced outcomes. Future research should focus on multi-center randomized controlled trials, incorporating long-term follow-up, advanced neuroimaging, and additional neuroprotective strategies. Comparative studies with other minimally invasive techniques, predictive modeling using AI, and biomarker discovery could further refine treatment approaches.

Disclosure of conflict of interest

None.