Background: Despite ongoing advances in critical care mortality and morbidity of patients
with subarachnoid hemorrhage remains high. Secondary brain injuries related to cerebral
vasospasm and consecutive ischemic brain injury and intracerebral edema are the main
contributors to mortality and morbidity in these patients. Evidence points towards low
serum sodium levels being one of the significant risk factors for of secondary brain
injury in this population. Previous studies show that fluid resuscitation with normal
saline results in higher serum sodium levels and higher serum osmolality when compared to
balanced infusates in patients with subarachnoid hemorrhage.
Aim: The primary objective of this study is to evaluate whether the use of a sodium-rich
infusion (normal saline) results in better clinical outcome when compared to a
sodium-depleted infusion (lactated Ringer's) in patients with subarachnoid hemorrhage.
The primary endpoint will be the occurrence of clinically relevant vasospasm requiring
immediate treatment. In addition, the investigators will assess other relevant
complications such as long and short-term mortality, significant brain edema requiring
conservative therapy or/and operative hemicraniectomy, as well as further
patient-relevant outcomes such as days on organ support, postoperative infections, length
of stay and long-term disability/mortality.
Study intervention: All patients admitted to a participating hospital with the diagnosis
of intracerebral bleeding will be screened and if eligible, randomized to one of the
study arms. Individual patient's consent will be sought. Thereafter, patients will
receive only the allocated study fluid for fluid maintenance and resuscitation from study
inclusion until ICU/intermediate care (IMC) discharge. Neurological evaluation will be
performed hourly for the initial phase and thereafter two hourly. Serum sodium,
osmolality, fluid, water and electrolyte balance as well as acid-base homeostasis will be
evaluated daily. Further, specific assessment of renal, cardiac and immune function takes
place at 5 pre-specified time-points (day 1,3,7,10 and at ICU/IMC discharge).
After ICU/IMC discharge patients will be followed for evaluation of secondary endpoints.
Long-term disability will be assessed by telephone interview based on the modified the
Rankin-Scale and the Glasgow Outcome Scale Extended.
Sample Size: Sample size calculation was based upon the investigators' ICU's registry
data. In 2017, 44.38% patients with subarachnoid hemorrhage reached the predefined
endpoint of clinically relevant vasospasm requiring immediate intervention. A clinically
relevant effect size was determined to be an improvement in outcome of 15%. Based on
these results a patient number of n = 160 for each group was determined under estimation
of a 15% drop out rate.