Study design and participants
This study was a prospective registry designed to include consecutive patients with HICH. Only patients with mild to moderate intracerebral hemorrhage were eligible for this study. All subjects were recruited from the emergency department of Neurology, and hospitalized in the department of Neurology and Geriatric department of our hospital 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 intracerebral hemorrhage treatment guidelines (2015) 8. They were confirmed by cranial computed tomography (CT) with supratentorial hematoma without or only a small amount of intraventricular hemorrhage, and the amount of hematoma was less than 30 mL according to the Tada (ABC/2) formula 9, with midline shift < l cm. The vital signs of subjects were relatively stable when they admitted to the hospital. Conservative treatment plan was first adopted after admission with the consent of the family. Exclusion criteria included local infection of the lumber spine, severe liver and kidney dysfunction, pituitary tumor and all diseases associated with damage to visual pathways. Among 116 patients recruited from the emergency department of Neurology, the final sample size was 102 for this study. Because individuals were further excluded for the following reasons: hematoma enlargement requires surgery (n=9), intracranial aneurysm ruptured (n=2), transfer to the superior hospital (n=2), haematuria (n=1). Subjects were randomly divided into FVEP nICP monitoring group (experimental group) and the non-monitoring group (control group). This was in congruence with the local ethics committee requirements. The study was approved by the local ethics committees of our institutions, and subjects informed consent.
All HICH patients with elevated ICP were placed in a recumbent position, with elevation of the head of the bed to 30 degrees, kept the airway unobstructed, took sedatives as appropriate to keep the patients calm and kept the surrounding environment quiet, maintained the body temperature below 38.0 ℃and strictly controlled blood pressure. For HICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of the SBP to 140 mmHg. For HICH patients presenting with SBP >220 mmHg, antihypertension agents were intermittent or continuous intravenous administration until SBP to 140 mmHg. Clinical symptoms and signs were observed every 30 minutes. 20% mannitol (Sichuan Kelun Pharmaceutical Co.Ltd, Sichun, China, batch no. A17103207-1) was used in reducing the elevated ICP in patients with HICH. Cranial CT was reviewed within 24h after admission, and were re-examined at any time according to the changes of the patient's condition. Patients of the experimental group received the first FVEP noninvasive and lumbar puncture iICP measurement within 1 h after admission. ICP values were monitored by FVEP nICP monitoring device within 24 hours, 3th day, 7th day and 14th day after admission, and mannitol dosage was timely adjusted according to the level of ICP. According to ICP values, the cases were divided into groups as normal (5.0 to 15.0mmHg), mildly increased (15.1 to 20.0 mmHg), moderately increased (20.1 to 40.0 mmHg) and severely increased (more than 40.1 mmHg). 1 mmHg is converted to mmH2O by multiplying with 13.6. Patients with mildly elevated ICP were observed closely without using mannitol. Patients with moderate elevated ICP lasting more than 10 minutes were offered 125 ml 20% mannitol, every 8 hours. The patients with severely elevated ICP were offered 125 ml 20% mannitol, every 6 hours. ICP values of patients in the control group were not monitored. The usage amount of mannitol was adjusted according to clinical symptoms, signs, hematoma size shown by CT. Mannitol, 125 ml 20% every 6 hours, was used in patients with consciousness disorders and hematoma enlargement by reviewing of cranial CT, and 125 ml 20% mannitol, every 8 hours in the other patients. The usage amount of mannitol and renal function were recorded in both groups. All patients were followed up to 3 months after discharge and their GOS scores were recorded.
FVEP non-invasive intracranial pressure monitoring
FVEP nICP was determined using the MIP-310 nICP monitor (Chongqing Haiweikang Medical Instrument Co. Ltd, Chongqing, China) before treatment within 1 h after admission. Patients were supine in quiet state, excluding mental factors and environmental interference. The grounding electrode (black line) was placed on the eyebrows, left record electrode (orange line) and the right record electrode (brown line) were respectively placed on the external occipital protuberance 2 cm, and the reference electrode (red line) was placed at the hairline. After wearing the eye mask, the subject was given flash stimulation (the light source was blue neon light with a frequency of 1.0 Hz and a pulse width of 2ms for 50 times). The latency and amplitude of N2 wave were recorded after the stimulation, then calculated the ICP. With the relation function between N2 wave and ICP: ICP=1.0371*latency-3.7106 (mmH2O), the ICP values of both left and right channels can be obtained. The testing process should be measured for 3 consecutive times within 15 min for each measurement, and the mean value of 3 times should be taken. The normal ICP range is 80-180 mmH2O, ≥ 200 mmH2O means the elevated ICP.
In our work, cerebrospinal fluid (CSF) lumbar pressure was used in this protocol as a surrogate measurement of ICP. After FVEP nICP monitoring, the lumbar puncture immediately operated in patients of experimental group in order to evaluate the accuracy of the FVEP nICP monitoring values. The patient was lying horizontally in the left lateral position. Once the appropriate location was palpated, after local anesthesia a non-traumatic lumbar needle was inserted in the L3-L4 or L4-L5 interspinous space and was left in place during the whole procedure. The CSF pressure was measured with a graduated fluid transducer. The zero reference pressure was the atmospheric pressure at the level of the foramen of Monro. In our study, local infection of the lumber spine and brain herniation were contraindications to lumbar puncture.
Clinical efficacy evaluation
Prognosis was evaluated using Glasgow Outcome Scale (GOS) standard 10. level 1: death; Level 2: plant survival state; Level 3: severely disabled, unable to take care of himself; Level 4: mild disability, self-care; Level 5: return to good health and normal life. Level 1 and level 2 were considered invalid, level 3 and level 4 were considered disabled, and level 5 was considered cured. Cure rate = number of patients of level 5 / total number of cases ×100%.
Statistical analysis was performed using SPSS software (Version 22.0, Chicago, IL, USA). Measurement data was given as mean ± standard deviation (S.D.) of the mean. Enumeration data was expressed as the count and percentage. Differences between study groups were examined with the χ2-test for categorical variables, and t-test for continuous variables. Pearson correlation analysis was used to analyze the correlation of ICP between the experimental group and the control group. P<0.05 was considered statistically significant.