Subarachnoid Hemorrhage Clinical Trial
Official title:
Impact of Herniation on WFNS Grading and Outcome in Spontaneous Subarachnoid Hemorrhage - a SWISS SOS Observational Trial
All patients (≥18 years) with a spontaneous SAH proven by computed tomography (CT), magnetic
resonance imaging (MRI) or lumbar puncture will be considered for this trial. Upon
presentation to a neurosurgical centre the patients will be treated according to the local
protocol. Upon admission the patient is clinically evaluated for occurrence of clinical signs
of brain herniation syndromes (anisocoria, bilateral dilated pupils, posturing). Usually
first line treatment includes neurological resuscitation (placement external cerebrospinal
fluid drainage in case of hydrocephalus, treatment of seizure, and general intensive care
measures). Hereafter, the patient is clinically evaluated for a second time. The patients
will be graded according to the usual WFNS scale and the modified "herniation WFNS" scale.
The whole treatment of the patient will be according to local clinical protocols. Outcome
will be measured at six and twelve months by trained investigators who are unaware of
clinical data. The primary endpoint is the difference of specificities of the WFNS and hWFNS
with respect to poor outcome (mRS 4-6) at 6 months after initial haemorrhage. Given that
specificity and sensitivity are negatively correlated, difference in sensitivity will be the
second primary outcome.
The null hypothesis to be tested is that the ratio of the true negative rates (specificity)
of the hWFNS and WFNS scores is 1.35 i.e. the new score will detect 35% more patients as
truly negative (good outcome) as compared to the old score. In addition and because of the
negative correlation between specificity and sensitivity we will also test that the ratio of
the true positive rate (sensitivity) is not below 0.82 i.e. the new score will not more than
18% less patients as truly positive (poor outcome).
Background
Aneurysmal subarachnoid hemorrhage (SAH) is a severe disease affecting approximately 400
patients per year in Switzerland. Death and severe disability after spontaneous SAH are
related to the initial severity of the bleeding. The scale which is most often used and
recommended to grade the severity of SAH is the World Federation of Neurosurgical Societies
scale. Besides the Glasgow Coma Scale as basis for the WFNS grading, the existence of a
neurologic deficit is included in this scale. In general WFNS I-III patients are termed good
grade and WFNS IV and V poor grade. Morbidity and Mortality after SAH should increase with
higher WFNS grade. Yet, despite low Glasgow Coma Scale (GCS) scores in poor grade SAH, 35 to
50% of aggressively treated patients show a favorable outcome.Even in the most severe SAH,
i.e. WFNS grade V, a good outcome is observed in 24 to 50% of patients treated aggressively,
which limits the usefulness of this scale for decisions such as whether to withhold or
continue treatment. Especially the differentiation between WFNS grade IV and WFNS grade V in
intubated patients is a huge problem. The reason for the discrepancy between poor grading and
favorable outcome is due to the difficulty of reliable GCS assessment in the acute stage of
SAH. In the acute stage the clinical status of the patient is distorted due to sedative
medication, seizure and hydrocephalus and does not necessarily display the "real" clinical
status. Therefore favorable outcome in poor grade SAH patients is not a matter of a very
beneficial course, but rather of an initial wrong WFNS grading.
The necessity of a reliable WFNS grading becomes evident when clinical decisions are made on
this basis or when scientific data of different studies has to be compared. With respect to
clinical decisions - usually WFNS grade V patients are not being treated due to the limited
capacity of surviving the SAH. Up to now there is no validated triage scheme to identify
which SAH patients will most likely not benefit from aggressive treatment based on WFNS
scores.
Because the GCS is the basis for WFNS grading, information about progressive herniation
beyond the motor response and posturing - e.g. third nerve dysfunction or loss of brain stem
reflexes - is unfortunately not incorporated in routine SAH grading. As a known consequence,
sedated and ventilated patients who do not exhibit a motor response but have symmetrically
reactive pupils and intact brain stem reflexes may be wrongly classified as having a GCS
score of 3 and thus a WFNS grade V, which leads to inaccuracies in the prognostic power of
the WFNS in poor grade patients.
In this study, the investigators will apply the concept following the logic of the original
GCS design and the pathophysiological concept behind the scale. During progression of brain
herniation, abnormal flexion (decorticate rigidity, late diencephalic syndrome) is followed
by abnormal extensor posturing (decerebrate rigidity, mesencephalic syndrome). Both are
positive signs, i.e. signs that can be observed by the examiner. If herniation further
progresses, damage occurs to the medulla and typical signs are flaccidity, no response to
pain, mydriasis and no reaction to light. Using the latter "positive" signs would help to
verify a true GCS 3 patient.
The purpose of this study is to re-evaluate the prognostic power of the WFNS classification,
particularly with regard to poor grade patients. The investigators compare the existing WFNS
grading with a modified WFNS herniation grading model (hWFNS) with respect to predicting poor
outcome and death.
Objective
The primary objective of this observational study is to test whether signs of herniation
(dilated unilateral or bilateral pupils, posturing) can improve the predictive value of poor
outcome at 6 months after SAH. Specifically, the study aims to show improved (superiority)
specificity of the modified scale while maintaining (non-inferiority) sensitivity.
Secondary objectives are the impact of radiological factors (general/focal brain edema,
intracerebral hematoma, hydrocephalus, amount of subarachnoid blood) as well as clinical
factors (seizure, timing of grading, sedation) and their impact on herniation and grading of
patients with SAH.
Methods
Patients with proven spontaneous SAH will be entered into the study. Upon presentation to a
neurosurgical centre the patients will be treated according to the local protocol. The
patient will be clinically assessed before and after neurosurgical resuscitation. Patients
are screened for occurrence of clinical signs of brain herniation syndromes. The patients
will be graded according to the usual WFNS scale and the modified "herniation WFNS" scale.
Outcome will be measured at six and twelve months by trained investigators who are unaware of
clinical data.
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