Standardized Criteria to Initiate External Ventricular Drain (EVD) Weaning in a Neurological Intensive Care Unit to Increase the Safety of EVD Discontinuation and Reduce the Need for a Shunt.

Introduction Patients with subarachnoid hemorrhages (SAH) with external ventricular drains (EVD) can develop chronic hydrocephalus (HCP), requiring permanent cerebrospinal fluid (CSF) diversion via an external shunt. Two different strategies have been used to assess for dependence on EVD: 1) prompt closure, and 2) gradual weaning. Gradual weaning of EVDs is performed by increasing drainage resistance to outflow over days. However, when to start one strategy or the other is up to the physician. No uniform guidelines exist raising a question: Are standardized criteria necessary to initiate the EVD weaning process for SAH patients to increase the safety of EVD discontinuation and reduce the need for a shunt? This study shares criteria used to initiate EVD weaning that displayed increased safety of EVD discontinuation for patients with subarachnoid hemorrhage requiring EVD, particularly with regards to length of hospital stay (LOS), hospital-acquired infection rates, and ventriculoperitoneal shunt/endoscopic third ventriculostomy (VPS/ETV) placement. Methods One hundred and fifty-one SAH patients from January 2016 to January 2019 were analyzed. 60 aneurysmal SAH (aSAH) and 18 non-aneurysmal nontraumatic SAH (naSAH) patients required EVD placement. A gradual EVD weaning protocol was initiated if patients met the following criteria: 1. The reason for EVD placement has resolved or is resolving, 2. The quantity of CSF output is <250mL over 24 hours, 3. Quality of CSF is nonbloody, 4. Intracranial Pressure (ICP) must be within normal limits, and 5. The patient must be neurologically stable. It was acceptable to initiate the weaning process when the patient had mild cerebral vasospasm, but not moderate to severe cerebral vasospasm. EVD weaning was performed by increasing the drain (chamber) height by 5 millimeters of mercury every 24 hours if the criteria were met. Charts were reviewed for LOS, infection rates, and rate of VPS/ETV. Gender, age, race, wean failure incidence, Hunt-Hess scores, modified Fisher scores, and syndrome of inappropriate antidiuretic hormone/cerebral salt wasting (SIADH/CSW) rates were obtained. Results The average LOS for aSAH patients with EVD was 20.35 days. The incidence of VPS/ETV was 11%. A chi-square analysis revealed that aSAH patients had higher rates of VPS/ETV placement (p<0.001) and EVD wean failures (p<0.001) than naSAH patients. aSAH patients had a lower incidence of VPS/ETV placement of 11% compared to 21% nationally. Conclusions Standardized criteria to initiate EVD weaning provided a reduction in VPS/ETV placement among aSAH patients compared to national averages and provided a uniform approach to EVD management. Comparable infection rates and LOS for SAH patients requiring EVDs compared to national averages were found.

Sigma 1 Receptor Co-Localizes with NRF2 in Retinal Photoreceptor Cells.

Sigma 1 receptor (Sig1R), a modulator of cell survival, has emerged as a novel target for retinal degenerative disease. Studies have shown that activation of Sig1R, using the high affinity ligand (+)-pentazocine ((+)-PTZ), improves cone function in a severe retinopathy model. The rescue is accompanied by normalization of levels of NRF2, a key transcription factor that regulates the antioxidant response. The interaction of Sig1R with a number of proteins has been investigated; whether it interacts with NRF2, however, is not known. We used co-immunoprecipitation (co-IP), proximity ligation assay (PLA), and electron microscopy (EM) immunodetection methods to investigate this question in the 661W cone photoreceptor cell line. For co-IP experiments, immune complexes were precipitated by protein A/G agarose beads and immunodetected using anti-NRF2 antibody. For PLA, cells were incubated with anti-Sig1R polyclonal and anti-NRF2 monoclonal antibodies, then subsequently with (-)-mouse and (+)-rabbit PLA probes. For EM analysis, immuno-EM gold labeling was performed using nanogold-enhanced labeling with anti-NRF2 and anti-Sig1R antibodies, and data were confirmed using colloidal gold labeling. The co-IP experiment suggested that NRF2 was bound in a complex with Sig1R. The PLA assays detected abundant orange fluorescence in cones, indicating that Sig1R and NRF2 were within 40 nm of each other. EM immunodetection confirmed co-localization of Sig1R with NRF2 in cells and in mouse retinal tissue. This study is the first to report co-localization of Sig1R-NRF2 and supports earlier studies implicating modulation of NRF2 as a mechanism by which Sig1R mediates retinal neuroprotection.