Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review.

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.

The Relationship Between Manifestation of Diabetes Insipidus and Estimated Glomerular Filtration Rate in Brain Death.

OBJECTIVES: Systematic reviews have revealed that up to 50% of patients with brain death have residual hypothalamic/pituitary activity based on the absence of central diabetes insipidus (DI). We hypothesized that different degrees of renal dysfunction may impact the presence of DI in patients with brain death. DESIGN: Single-center prospective data collection. SETTING: ICUs in a tertiary academic hospital. PATIENTS: All adult patients declared brain dead over 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: DI was diagnosed by polyuria, low urine specific gravity, and increasing serum sodium, measured in close proximity. Renal function was assessed by the estimated glomerular filtration rate (eGFR), calculated using the simplified modification of diet in renal disease equation. Analysis was completed in 192 of 234 patients with brain death after excluding those with missing data, those younger than 18 years and those on vasopressin infusions. One hundred twenty-two patients (63.5%) developed DI and 70 patients (36.5%) did not. The proportion of DI decreased significantly with decreasing eGFR: for eGFR greater than 60 mL/min, DI was present in 77.2%; for eGFR 15-60 mL/min, DI was present in 54.5%; for eGFR 14.9-9.8 mL/min, DI was present in 32%; none of the 14 patients with eGFR less than or equal to 9.7 mL/min ever experienced DI ( p < 0.001). Using logistic regression, for every 10 mL/min decrease in eGFR, the odds of DI decreased 0.83 times (95% CI, 0.76-0.90, p < 0.001). CONCLUSIONS: Renal dysfunction significantly impacts DI's clinical manifestation in brain death. We report that patients who experience brain death with severe renal dysfunction may not develop clinical signs of DI.

Comparison of 1 vs 2 Brain Death Examinations on Time to Death Pronouncement and Organ Donation: A 12-Year Single Center Experience.

OBJECTIVE: To fill the evidence gap on the value of a single brain death (SBD) or dual brain death (DBD) examination by providing data on irreversibility of brain function, organ donation consent, and transplantation. METHODS: Twelve-year tertiary hospital and organ procurement organization data on brain death (BD) were combined and outcomes, including consent rate for organ donation and organs recovered and transplanted after SBD and DBD, were compared after multiple adjustments for covariates. RESULTS: A total of 266 patients were declared BD, 122 after SBD and 144 after DBD. Time from event to BD declaration was longer by an average of 20.9 hours after DBD (p = 0.003). Seventy-five (73%) families of patients with SBD and 86 (72%) with DBD consented for organ donation (p = 0.79). The number of BD examinations was not a predictor for consent. No patient regained brain function during the periods following BD. Patients with SBD were more likely to have at least 1 lung transplanted (p = 0.031). The number of organs transplanted was associated with the number of examinations (ß coefficient [95% confidence interval] -0.5 [-0.97 to -0.02]; p = 0.044), along with age (for 5-year increase, -0.36 [-0.43 to -0.29]; p < 0.001) and PaO2 level (for 10 mm Hg increase, 0.026 [0.008-0.044]; p = 0.005) and decreased as the elapsed time to BD declaration increased (p = 0.019). CONCLUSIONS: A single neurologic examination to determine BD is sufficient in patients with nonanoxic catastrophic brain injuries. A second examination is without additional yield in this group and its delay reduces the number of organs transplanted.

Ultra-Early Venous Thromboembolism (VTE) Prophylaxis in Spontaneous Intracerebral Hemorrhage (sICH).

OBJECTIVE: To determine if ultra-early (<24 h) venous thromboembolism (VTE) prophylaxis was associated with hematoma growth in spontaneous intracerebral hemorrhage (ICH). BACKGROUND: Patients with ICH have a high risk of VTE. Pharmacological prophylaxis such as unfractionated heparin (UFH) have been demonstrated to reduce VTE. However, published datasets exclude patients with recent ICH out of concern for hematoma enlargement. American Heart/Stroke Association guidelines recommend UFH 1-4 days after hematoma stabilization while the European Stroke Organization has no recommendations on when to begin UFH. Our institutional practice is to obtain stability CT scans at 6 to 24 h and to begin UFH following documented clinical and radiologic stability. We examined the impact of this practice on hematoma expansion. METHODS: We performed a retrospective cohort analysis of consecutive ICH patients treated at a single tertiary academic referral center in the US. Demographic and clinical characteristics were abstracted. ICH volume was measured via 3D volumetrics for a CT head done on admission, follow-up stability, and prior to discharge. The primary outcome was analyzed as ≥3 mL hematoma enlargement. Secondary outcomes include hematoma expansion of ≥6mL and ≥ 33%, length of stay (LOS), discharge disposition and mortality. RESULTS: A total of 163 ICH patients were analyzed. There were 58 (35.6%) patients in the ultra-early UFH group and UFH was initiated on average at 13.8 h from initial scan. There were 105 (64.6%) patients in the standard group who initiated UFH at an average of 46.6 h. The primary outcome of hematoma enlargement ≥3 mL was observed in 2/58(3.4%) patients with ultra-early initiation of UFH and in 7/105(6.7%) in the standard group (p=0.49). Secondary outcomes were not significant including hematoma expansion in the ultra-early group ≥ 6 mL 3/58 (5.2%) and ≥33% 7/58 (12.1%) (p=0.91, 0.61, respectively) as well as mortality or LOS. CONCLUSION: Venous thromboembolism prophylaxis started ultra-early (≤24 h) after ICH was not associated with hematoma expansion.

Arterial and venous strokes in the setting of COVID-19.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is a global pandemic that causes flu-like symptoms. There is a growing body of evidence suggesting that both the central and peripheral nervous systems can be affected by SARS-CoV-2, including stroke. We present three cases of arterial ischemic strokes and one venous infarction from a cerebral venous sinus thrombosis in the setting of COVID-19 infection who otherwise had low risk factors for stroke. METHODS: We retrospectively reviewed patients presenting to a large tertiary care academic US hospital with stroke and who tested positive for COVID-19. Medical records were reviewed for demographics, imaging results and lab findings. RESULTS: There were 3 cases of arterial ischemic strokes and 1 case of venous stroke: 3 males and 1 female. The mean age was 55 (48-70) years. All arterial strokes presented with large vessel occlusions and had mechanical thrombectomy performed. Two cases presented with stroke despite being on full anticoagulation. CONCLUSIONS: It is important to recognize the neurological manifestations of COVID-19, especially ischemic stroke, either arterial or venous in nature. Hypercoagulability and the cytokine surge are perhaps the cause of ischemic stroke in these patients. Further studies are needed to understand the role of anticoagulation in these patients.

The effect of race on clinical presentation and outcomes in neurosarcoidosis.

BACKGROUND: Nervous system is affected in 25% of patients with sarcoidosis. Current literature is largely limited to case reports with disproportionate Caucasian population. We aim to evaluate differences in presentation, management and outcomes by race in neurosarcoidosis. METHODS: Clinical and demographic data on consecutive patients fulfilling Zajicek criteria for neurosarcoidosis from 1995 to 2016 at Henry Ford Hospital were extracted. Disparities in clinical presentation, laboratory values, radiological features, treatment and outcomes, were compared between two groups: African Americans (AA) and non-AA using chi-squared tests, two sample t-test for age and Wilcoxon two sample tests. RESULTS: A total of 118 patients were included, of which 58% were female and 73% were AA. The diagnosis of neurosarcoidosis was noted to be definite (25%), probable (64%) and possible (11%). AA patients had a significantly higher rate of elevated erythrocyte sedimentation rate (62% vs 24%, P = .005) and had lower resolution of abnormalities on follow-up imaging (14% vs 41%, P = .017). There was no difference in disability on follow-up (25% vs 33%, P = .43) or mortality (13% vs 9%, P = .6). CONCLUSIONS: There were no differences in presentation, management and outcomes by race. Discordance in the clinical and radiological data by race has clinical implications and needs further investigation.

Factors that affect consent rate for organ donation after brain death: A 12-year registry.

OBJECTIVE: To account for factors affecting family approach and consent for organ donation after brain death (BD). MATERIAL AND METHODS: A prospective cohort study in a large, tertiary, urban hospital, where we reviewed the database of all brain-dead patients between January 2006 and December 2017 cross-matched with local organ procurement organization (OPO) records. RESULTS: Two-hundred sixty-six brain-dead patients were included (55% African Americans (AAs)). Two-hundred twenty-two were approached for donation. The reason for not approaching families was medical exclusion due to cancer or multi-organ failure. Patient demographics or religion were not associated with approaching families. Lower creatinine level was the only independent factor associated with higher approach. Consent rate for organ donation was 72.5%. Consent was significantly higher in Caucasians (89% vs 62% for AAs), younger patients (46.7 vs 52.5 years old), in patients with lower creatinine at time of death (1.7 vs 2.4 mg/dL), patients for whom apnea testing was completed (92% vs 80%) and patients with diabetes insipidus (DI) (72% vs 54%). There was no significant relationship between consent and patient gender, admission diagnosis, number of examinations or completion of a confirmatory test. In a logistic regression model, only AA race independently predicted consent for donation (odds, 95% CI, 0.27, 0.12-0.57 p < .001). In a different model, apnea test completion was an additional independent predictor (3.66, 1.28-10.5 p = .015). CONCLUSIONS: Approaching families for organ donation consent was associated with medical suitability only and not with demographic or religious characteristics. AAs were 3.7 times less likely to consent for organ donation than non-AAs. Completion of apnea testing was associated with higher consent rates, an observation that needs to be explored in future studies documenting the effect on bedside family presence during this test.