Abstract
BackgroundWe demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH.MethodsSAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO2) increased by > 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS).ResultsSeven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO2 time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died.ConclusionAdministration of iNO in SAH patients is safe. These results call for a larger prospective evaluation.
Highlights
Despite advances in emergency medicine, neurocritical care, and aneurysm occlusion techniques, aneurysmal subarachnoid hemorrhage remains a rare but severe subtype of stroke with high mortality and poor outcome [1, 2]
Inclusion criteria were aneurysmal subarachnoid hemorrhage (aSAH) of all severities [World Federation of Neurosurgeons (WFNS) score I–V], aneurysm treated by either surgical clipping or endovascular coiling, age between 18 and 80 years, proven Cerebrovascular spasm (CVS), delayed cerebral ischemia and neurological deficit despite treatment, a negative pregnancy test in women, and signed informed consent from the of kin and an independent physician
The primary endpoint of this study was improvement of severe vasospasm, as indicated by any of the following prespecified criteria: digital subtraction angiography (DSA): a > 10% increase in diameter of the vasospastic target vessel compared to baseline; PtiO2: an increase of more than 5 mmHg with constant fraction of inspired oxygen (FiO2); transcranial Doppler (TCD): a decrease of more than 30 cm/s; CTP: a reduction in the number of regions of interest (ROIs) with impaired perfusion (MTT > 6.5 s)
Summary
Despite advances in emergency medicine, neurocritical care, and aneurysm occlusion techniques, aneurysmal subarachnoid hemorrhage (aSAH) remains a rare but severe subtype of stroke with high mortality and poor outcome [1, 2]. Delayed cerebral ischaemia (DCI) is thought to be the major reason for poor outcome in survivors of aSAH [2] Up to this day and despite decades of iNO for Aneurysmal Subarachnoid Hemorrhage experimental and clinical research, causes and pathomechanisms of DCI are still not completely clear and most probably multifaceted [3]. In patients with critical cerebral hypoperfusion without established cerebral infarction, rescue therapies such as induced hypertension, intra-arterial application of vasodilators, or angioplasty are used to improve cerebral perfusion The efficacy of such interventions is not proven, their effects are temporary at best, and adverse effects are possible, including exposure to radiation [6,7,8].
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