Clinical Application of ICP Monitoring Based on FVEP in Treatment of Patients with Hypertensive Intracerebral Hemorrhage

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Abstract Objective
To investigate the application value of ash visual evoked potential (FVEP) in the monitoring of the noninvasive intracranial pressure (nICP) in patients with hypertensive intracerebral hemorrhage (HICH).

Methods
One hundred and two patients with HICH were randomly divided into FVEP nICP monitoring group (experimental group) and the non-monitoring group (control group). The experimental group were examined lumbar puncture immediately after intracranial pressure was monitored by FVEP. Mannitol was used to dehydration treatment of intracranial hypertension patients. The serum concentrations of creatinine and urea nitrogen were recorded to assess the renal function. Using the mannitol usage to evaluate the value of FVEP nICP monitoring techniques in guiding the adjustment of dehydrating agent. The Glasgow prognosis scores (GOS) were evaluated for patients' prognosis between two groups.

Results
There was no statistical signi cance between FVEP nICP measurement and lumbar puncture intracranial pressure measurement (195.76 ±13.24 mmH 2 O vs 197.04 ±11.98 mmH 2 O, P>0.05). The use of mannitol in the experimental group was signi cantly lower than that in the control group (P< 0.05), and the serum creatinine and urea nitrogen concentrations in the two groups were not statistically signi cant (P> 0.05).
The cure rate of the experimental group was higher than that of the control group (χ 2 =3.889, P=0.048).

Introduction
Hypertension intracerebral hemorrhage (HICH) with the characteristic of high morbidity, mortality and disability is one of the major diseases that endanger the health of the elderly [1]. High intracranial pressure (ICP) caused by HICH is a common critical condition in neurology. The increase of ICP leads to the displacement of local brain tissue or the formation of brain herniation, which is the direct cause of the rapid deterioration of patients' condition and even death [2]. Headache, vomiting, and decreased levels of consciousness are the symptoms of increased ICP, but these clinical symptoms are not speci c. At present, most of the ICP monitoring methods are invasive. Some limitations of the invasive methods include short-term monitoring, risk of infection, restricted mobility of the subject, etc [3]. Therefore, it is necessary to nd a noninvasive and reliable monitoring method. Noninvasive intracranial pressure (nICP) monitoring technology may replace invasive intracranial pressure (iICP) to help clinical diagnosis and treatment. Flash visual evoked potential (FVEP) has been widely applied in clinical diagnosis due to its noninvasive and easy to operate. Most clinical studies on FVEP nICP monitoring technology focus on patients with craniocerebral trauma, subarachnoid hemorrhage and HICH induced ICP elevation. HICH is the most common disease of increased ICP in neurology department. Mannitol is usually used to dehydration treatment of intracraninal hypertension patients, but it can also cause side effects such as renal function damage and electrolyte disorder. In addition, under pathological conditions, mannitol crystals can form a hypertonic state locally through penetrating the damaged blood-brain barrier and aggravate cerebral edema [4]. This study aims to monitor the changes of ICP in HICH patients with FVEP nICP monitoring technology, and help to adjust the dosage of dehydrating agent, shorten the clinical treatment time, improve the prognosis of HICH patients, and reduce the economic burden of patients.

Participants
One hundred and two patients HICH were enrolled from the department of neurology and geriatrics from November 2016 to December 2017. All subjects who had a history of hypertension or elevated blood pressure at onset met the diagnostic criteria of the American adult ICH treatment guidelines (2010) [5].
Cranial computed tomography (CT) showed supratentorial hematoma without or only a small amount of intraventricular hemorrhage. The amount of hematoma was less than 30 mL according to the multi-eld formula, with midline shift < l cm. When admitted to the hospital, their vital signs were relatively stable, and they did not have previous visual impairment. Conservative treatment plan was rst adopted after admission with the consent of the family.

Comparison of renal function and mannitol usage amount between two groups
There were two cases who suffered kidney dysfunction in the control group, manifested as elevated creatinine and urea nitrogen values, but no statistical signi cance was found between the experimental group and the control group (P > 0.05). Compared with the control group, the amount of mannitol usage in the experimental group was signi cantly decreased (P < 0.05) ( Table 1).

Comparison of GOS scores between two groups
There were 35 patients with GOS grade 5 in the experimental group and 23 patients with GOS grade 5 in the control group. The cure rate in the experimental group was higher than that in the control group (67.3% vs. 46.0%, χ 2 =3.889, P=0.048) ( Table 2).

Discussion
Raised ICP after intracerebral hemorrhage plays an important role in secondary brain injury and is associated with increased mortality [7]. Timely detecting of ICP changes is the key to successful rescue of critically ill patients. Nowadays, most methods of ICP monitoring are invasive, but it's more likely to occur intracranial infection, intracranial hemorrhage and other complications. Mizutani et al. [8] attempted to evaluate the sizes of intracranial hematoma, subdural hematoma, ventricular, and the degrees of subarachnoid hemorrhage and brain trauma injury through CT imaging, and established the relationship equation between CT imaging and increased ICP by applying multiple regression analysis.
But the results showed that the error of ICP value was more than 40 mmH 2 O. Magnetic resonance imaging (MRI) examination is not convenient to be used in critically ill patients, nor can it be used to monitor ICP in a timely and dynamic manner [9,10]. FVEP nICP monitoring technology had been applied in clinical practice since 1986 [11]. FVEP is the electrical activity generated by the occipital cortex to the visual stimulation induced by the diffuse non-mode light source. The delay time of the second negative wave (N2 wave) of the brain FVEP is directly related to ICP. A microcomputer device can be used to perform visual stimulation and measure the delay time of N2 wave, then we can obtained the ICP value by comparing the relation table of N2 wave delay time and ICP value [12]. York et al. con rmed in the study of pediatric hydrocephalus and non-open craniocerebral trauma that there was a strong linear relationship between increased ICP and prolonged latency of N2 wave of visual evoked potential (the correlation coe cient was 0.8-0.9) [13]. Visual evoked potential is best predicted when cranial hypertension is greater than or equal to 300 mmH 2 O [14].
Our research showed that there was an error between the monitoring values of invasive and noninvasive ICP in patients with HICH, but the difference was not statistically signi cant. Therefore, FVEP nICP monitoring technology can be widely used in the clinical monitoring of HICH patients. The majority of patients with intracerebral hemorrhage experienced further increase in ICP due to hematoma enlargement within 24h after the onset of intracerebral hemorrhage. Some researchers showed that the increase of ICP is signi cantly earlier than the clinically observed changes in consciousness and vital signs [15,16]. Especially applicable to patients with mild to moderate HICH without invasive ICP monitoring, FVEP nICP monitoring technology can be used as an effective means of early warning of further increase of ICP and further enlargement of hematoma. Moreover, traditional lumbar puncture manometry is forbidden in patients with severe high cranial pressure (intracranial pressure greater than 350 mmH 2 O) , because it is likely to induce cerebral hernia. Therefore, the use of FVEP nICP monitoring is particularly important for HICH patients, especially for monitoring the change of ICP on the hematoma side, for evaluating the degree of cerebral hemorrhage and cerebral edema, and for early understanding of the dynamic changes of hematoma.
In HICH patients, intracranial hematoma and cerebral edema will lead to intracranial hypertension in 70% of patients. If not timely intervention will seriously affect the recovery of neurological function and prognosis of patients. Currently, mannitol is the most commonly dehydrating agents which lower ICP by reducing blood viscosity and increasing plasma osmotic pressure [17]. However, clinical usage amount lacks scienti c standards and often relies only on clinical experience, as for mannitol to achieve the expected effect is more di cult to determine. In addition, mannitol can cause kidney function damage and electrolyte disturbance. In order to reduce the possible damage caused by using of high doses of mannitol blindly, the American stroke Association recommends that mannitol should not be used prophylactically and should not be used for more than 5 days during rst aid [18,19].
Clinical data showed that mannitol could shorten the incubation period of FVEP N2 wave, and FVEP could observe the changes of ICP after mannitol application [20]. In our experiment, the dynamic changes of ICP in the experimental group were monitored by FVEP nICP monitoring technology, and the using frequency of mannitol was timely adjusted. The amount of mannitol was signi cantly less than the control group. The complications of kidney function impairment caused by drugs were also rare than those in the control group. The ICP changes monitored by FVEP nICP monitoring technology can accurately guide clinical treatment. Moreover, ICP changes in patients with HICH can be detected timely. It means that FVEP nICP monitoring plays an important early warning role in the treatment of severe craniocerebral injury, and can effectively guide the clinical active use of dehydrating agent and craniotomy.
Our research showed that the recovery rate of the experimental group was signi cantly higher than that of the control group, and the prognosis of the HICH patients could be improved by closely monitoring the change of ICP value and timely adopting reasonable treatment plan.
In conclusion, FVEP nICP monitoring technology has the advantages of noninvasive, simple operation and reliable results, and can replace the traditional invasive ICP monitoring methods in patients with HICH. The dynamic monitoring of ICP in HICH patients can guide the clinical timely adjustment of the dosage of mannitol and improve the condition and prognosis of HICH patients. However, the limitations and in uencing factors of FEVP nICP monitoring technology should also be considered during clinical use, so as to better understand its indications and provide more reliable methods and means for clinical treatment of patients with HICH intracranial hypertension.