Application of Magnesium-rich Artificial Cerebrospinal Fluid in Aneurysmal Subarachnoid Hemorrhage
Application of Magnesium-rich Artificial Cerebrospinal Fluid in Aneurysmal Subarachnoid Hemorrhage
Aneurysmal subarachnoid hemorrhage (aSAH) is a common type of acute hemorrhagic stroke. One
 of its complications, cerebral vasospasm (CVS), is the main cause of death and disability,
 with an incidence of up to 30%-90%. Blood and its metabolites are vital reasons for CVS.
 Normal saline, as an intraoperative irrigation fluid for the surgery of aneurysm clipping,
 can induce secondary damage to the brain. In this study, a new type of magnesium-rich
 artificial cerebrospinal fluid (MACSF) has been designed, which has similar ionic
 concentration, pH value and osmotic pressure compared with the physiological cerebrospinal
 fluid. It has been confirmed by animal experiments that MACSF can relieve the
 hyper-responsiveness of cerebral arteries to ET and 5-HT induced by hemorrhagic CSF from
 patients with aSAH by down-regulating the expression of ETA, contractile ETB and 5-HT1B
 receptors in the previous research. Therefore, MACSF may have potential effects on preventing
 and treating CVS. In this study, we plan to apply MACSF as an intraoperative irrigation fluid
 for the surgery of aneurysm clipping (MACSF group), which is compared with normal saline
 (historical control group). To evaluate the effects of MACSF on reducing the incidence of CVS
 and improving the clinical prognosis of patients with aSAH, the occurrence of CVS within 14
 days after aneurysm clipping, NIHSS score, as well as mRS scores at 1, 3 and 6 months after
 aSAH will be recorded and compared. CVS related biomarkers will be used to evaluate the
 relationship between the occurrence of CVS and the levels of biomarkers in both CSF and blood
 samples from MACSF group.
From now on, participants who meet the inclusion and exclusion criteria in our hospital will
 be recruited in the intervention group, if they and their relatives are willing to join in
 the study. For the historical control group, in which patients were treated by aneurysm
 clipping in Department of Neurosurgery of the First Affiliated Hospital of Xi'an Jiaotong
 University during the previous nine months, normal saline (0.9% Sodium Chloride Injection)
 was applied as intraoperative perfusion solution for their operation. For the intervention
 group, MACSF will be used. (The composition and concentration of MACSF is as follows: Na+:
 146.2 mEq/l, K+: 2.7 mEq/l, Mg2+: 4.2 mEq/l, Cl-: 123 mEq/l, HCO3-: 23.2 mEq/l, Glucose: 0.75
 g/l. MACSF is prepared by the staff of Pharmacy Intravenous Admixture Services of First
 Affiliated Hospital of Xi'an Jiaotong University, according to a specific formula in the
 specific working area. The whole procedure follow the aseptic principles strictly. Fresh-made
 MACSF will be placed in a specific container and send to the operating room through specific
 channels.) Then, for the patients who have signed the informed consent, blood (6ml) and CSF
 (3ml) samples will be collected during and every other day after the surgery for 14 days. The
 blood samples should be drawn into a non-anticoagulant tube and a heparin anticoagulant tube
 respectively. All the samples will be transferred to BioBank of the First Affiliated Hospital
 of Xi'an Jiaotong University in a liquid nitrogen tank. After re-melted in a water bath of
 37℃, the CSF and blood samples will be centrifuged at 4℃ for 10min at 2000r/min, and then the
 supernatant will be collected and stored at -80℃. At the end of this study, the contents of
 NPY，MMP-9，MIF，TNF-α，Mg2+ and Ca2+in the samples will be detected by ELISA or mass
 spectrometry. Transcranial Doppler (TCD) will be observed within 14 days after the operation
 (daily for the first three days and every other day for the following days). CVS will be
 diagnosed by TCD, the diagnostic criteria will be described later. CT scan of the brain
 should be done at least once a week and rechecked anytime when necessary. If there is new
 low-density lesions, delayed cerebral infarction (DCI) will be diagnosed. The prognosis will
 be assessed at 1, 3 and 6 months after aSAH onset according to modified Rankin Scale (mRS) .
 Meanwhile, some indicators will be used to evaluate the safety of MACSF application, which
 incluiding secondary infection, fluctuation of intracranial pressure and hypermagnesemia. The
 diagnostic criteria and the solutions will be described in the next part.
Inclusion Criteria:

 -  Patient is between 18 and 80 years of old;

 -  aSAH is diagnosed by CTA, DSA or other cranial imaging examination;

 -  Patient is admitted to hospital within 72 hours after aSAH onset;

 -  Aneurysm is clipped within 36 hours after admission;

 -  Patient and his/her relatives are informed and agree to accept the above treatment
 plan.

 Exclusion Criteria:

 -  Cause of the SAH is not rupture of an intracranial aneurysm;

 -  Time from SAH onset to admission is longer than 72 hours;

 -  Time from admission to surgery is longer than 36 hours;

 -  The patient dose not choose clipping;

 -  Patient has other serious diseases, such as heart failure, kidney failure, liver
 failure, etc;

 -  Patient or his/her relatives refuse to accept the above research plan.