Single institution experience with death by neurological criteria/brain death guideline adherence.

OBJECTIVE: To determine the effect on adherence to an institutional death by neurological criteria/brain death (DNC/BD) policy of implementation of a standardized DNC/BD checklist in the electronic medical record (EMR). METHODS: The retrospective study cohort included all patients admitted to our institution who were declared dead by neurologic criteria determined by ICD code (G93.82) between June 2015 and October 2019. Two investigators independently reviewed each case for adherence with institutional policy, and agreement was assessed using unweighted kappa statistics. Patient data and adherence to institutional policy before and after implementation of a standardized DNC/BD checklist were compared. RESULTS: There were 66 patients identified by the initial search and 38 were included in the final analysis, with 19 cases in both the pre- and post- checklist periods. There were no significant differences in age, cause of DNC/BD, time to DNC/BD determination, potential toxic, metabolic, physiologic confounders, or use of ancillary testing. The pre-checklist period adherence was 47.4% (n = 9/19) versus 94.6% (n = 18/19; p = 0.001) in the post-checklist EMR DNC/BD period. CONCLUSION: Implementation of a standardized EMR checklist substantially improved DNC/BD policy adherence in our institution. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the use of standardized EMR checklist to improve death by neurologic criteria/brain death policy adherence.

Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Metabolic values precluding clinical death by neurologic Criteria/Brain death: Survey of neurocritical care society physicians.

BACKGROUND: There are no established ranges for metabolic values prior to death by neurologic criteria/brain death determination (DNC/BD) and the thresholds required by institutional protocols and accepted by neurointensivists is unknown. METHODS: We designed a survey that addressed 1) the metabolic tests required in institutional guidelines prior to brain death determination, 2) the metabolic tests the respondent reviewed prior to brain death determination, and 3) the metabolic test thresholds for laboratory tests that were perceived to preclude or permit clinical DNC/BD determination. The survey was distributed online to physicians in the Neurocritical Care Society from September to December 2019. Respondents were dichotomized based on the number of brain death evaluations they had performed (≤20 vs. > 20) and responses were compared between groups. RESULTS: The survey was completed by 84 physicians. Nearly half (47.6%) of respondents did not believe their institutions required metabolic testing. The metabolic testing for which institutions most commonly provided a defined threshold were arterial pH (34.5%, 29/84), sodium (28.6%, 24/84), and glucose (15.5%, 13/84). Nearly all (97.6%) respondents routinely reviewed metabolic tests prior to brain death evaluation, the most common of which were: sodium (91.7%, 77/84), arterial pH (83.3%, 70/84), and glucose (79.8%, 67/84). Respondents who had performed > 20 evaluations were less likely to check thyroxine and total bilirubin (3.6%, 2/55 vs. 20.7%, 6/29 (p = 0.011) and 12.7%, 7/55 vs. 31%, 9/29 (p = 0.042), respectively), and had a more liberal upper limit of potassium (6.3 mEq/L vs 6.0 mEq/L, p = 0.045). CONCLUSION: Prior to brain death evaluation, neurocritical care providers commonly review similar metabolic tests and have similar thresholds regarding values that would preclude clinical brain death determination. This finding is independent of experience with brain death determination.

Brain Herniation and Intracranial Hypertension.

This article introduces the basic concepts of intracranial physiology and pressure dynamics. It also includes discussion of signs and symptoms and examination and radiographic findings of patients with acute cerebral herniation as a result of increased as well as decreased intracranial pressure. Current best practices regarding medical and surgical treatments and approaches to management of intracranial hypertension as well as future directions are reviewed. Lastly, there is discussion of some of the implications of critical medical illness (sepsis, liver failure, and renal failure) and treatments thereof on causation or worsening of cerebral edema, intracranial hypertension, and cerebral herniation.

Toxin-Induced Subacute Encephalopathy.

Subacute toxic encephalopathies are challenging to identify due to their often insidious tempo of evolution, nonspecific manifestations, relative infrequency as individual entities, and frequent lack of specific diagnostic testing. Yet they are crucial to recognize-in aggregate, subacute toxic encephalopathies are a common problem that can lead to severe, irreversible harm if not diagnosed and treated efficiently. This article reviews the clinically relevant aspects of some of the more important subacute toxic encephalopathy syndromes caused by inorganic toxins, carbon monoxide, antibiotics, antineoplastic agents, and psychiatric medications.

The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression.

Nonlinear chromatin configurations can juxtapose widely separated elements within a genomic locus; however, it remains unclear how these structures are established and contribute to transcriptional control. A 5'-remote locus control region (LCR) regulates the human growth hormone (hGH-N) gene. HSI, a pituitary-specific component of the hGH LCR, establishes a domain of polymerase II (PolII) transcription 5' to hGH-N. Repression of this transcriptional domain by HSI deletion or PolII blockade decreases hGH-N expression. Here, we show that hGH-N activation is accompanied by positioning of the hGH-N promoter to this LCR transcriptional domain. Selectively blocking LCR transcription inhibits the formation of this active 'looped' conformation. Thus, HSI is crucial for establishing a domain of noncoding PolII transcription, and this domain is intimately linked with chromatin organization of the active hGH-N locus. This integration of LCR transcription with chromatin reconfiguration constitutes a robust pathway for long-range gene activation.