Phenytoin prophylaxis and functional outcomes following spontaneous intracerebral hemorrhage: A systematic review and meta-analysis.

INTRODUCTION: Seizure activity following spontaneous intracerebral hemorrhage (sICH) can worsen patients' comorbidity. However, data regarding whether seizure prophylaxis for sICH is associated with patients' poor functional outcome is inconclusive. We performed a systematic review and meta-analysis to assess the relationship between phenytoin prophylaxis and poor functional outcome after sICH. METHODS: We conducted our search on PubMed, Scopus, and EMBASE databases as of October 30, 2020 for studies that included information on seizure prophylaxis and functional outcome in patients with sICH. Primary outcome was poor functional outcome at the longest follow-up in patients receiving seizure prophylaxis. The secondary outcome was poor functional outcome at 90 days follow-up. We conducted random effects meta-analysis and moderator analyses to detect sources of heterogeneity for our outcomes. RESULTS: We included eleven studies in the final analysis with a total of 4268 patients. A moderator analysis further showed prospective studies had lower heterogeneity. We did not find an association between seizure prophylaxis and poor functional outcome at time of longest follow-up (OR 1.2, 95%CI 0.9-1.6, p-value = 0.22, I2 = 61%), nor at 90-day follow-up (OR 1.4, 95%CI 0.8-2.4, p-value = 0.24, I2 = 78%). CONCLUSION: Seizure prophylaxis following sICH was not associated with worse functional outcomes at longest follow-up or at 90 days. Neither levetiracetam nor phenytoin was associated with outcome in our exploratory meta-regression, though there is a trend towards better outcomes in populations where there was a higher percentage of patients who received levetiracetam. More randomized trials are needed to confirm this observation.

Preventing seizure occurrence following spontaneous intracerebral haemorrhage: A systematic review and meta-analysis of seizure prophylaxis.

INTRODUCTION: Spontaneous intracerebral haemorrhage (ICH) is associated with high mortality and high morbidity, including seizures. Seizure prophylaxis is "not recommended" by the American Stroke Association, but practice variation still exists due to inconclusive data. We performed a meta-analysis to assess the current relevant literature to determine the efficacy of seizure prophylaxis following ICH. METHODS: We performed searches of PubMed, Scopus, and Embase up to September 15, 2020. We included observational and randomized controlled studies reporting seizure prophylaxis and occurrence in adults with ICH. Outcomes were seizures, as defined by the authors, within 14 days of ICH and at the longest point of follow-up. We used random-effects models to estimate the odds ratios (ORs) for seizure prophylaxis and outcomes. The PROSPERO registration was CRD42019140493. RESULTS: We included 8 studies (2852 patients) in our analysis. The mean (± standard deviation) age of the pooled patients was 65 (±4) years; 39 % (± 5%) were female. Seizure prophylaxis did not prevent seizures at the longest follow-up time (OR 0.708, 95 % CI 0.438-1.143, p = 0.158, I2 = 34 %). This result was confirmed in subgroup analyses using categorical variables and in meta-regressions using continuous variables. Additionally, seizure prophylaxis was not associated with preventing early seizures, defined as < 14 days of ICH (OR 0.66, 95 % CI 0.21-2.08, p = 0.48, I2 = 35 %). CONCLUSION: Seizure prophylaxis following ICH was not associated with seizure prevention in adults. Most included studies were observational. Further randomized controlled trials examining the efficacy of seizure prophylaxis in high-risk patients and different types of antiepileptic drugs are needed.

Calcium Alkali Thiazide Syndrome: What We Need to Know.

Depending on each institution's laboratory test, mean serum calcium levels range between 8.8 and 10.8 mg/dL and hypercalcemia is defined as two standard deviations above the mean. According to recent epidemiological studies, 90% of cases of hypercalcemia are due to hyperparathyroidism or malignancy. Milk Alkali syndrome (MAS) also known as Calcium Alkali syndrome (CAS) is the third biggest cause of hypercalcemia, but its incidence seems to be higher than previously thought. Here we present a case of Calcium Alkali Thiazide syndrome (CATS) in a 57-year-old female who was on calcium and vitamin D supplements (after parathyroidectomy) while also taking thiazide diuretic for hypertension. She was brought to the ED with nausea, vomiting, confusion, difficulty walking along with numbness in extremities. She had parathyroidectomy three weeks ago. During history taking, patient reported intake of calcium carbonate 1 g three times daily, calcitriol 0.5 mcg twice daily, cholecalciferol (vitamin D3) 10,000 units once daily, chlorthalidone 25 mg once daily and irbesartan 300 mg once daily. At admission, her calcium level was 23 mg/dL, ionized calcium 12.03 mg/dL, pH was 7.59 and HCO3 was 33. She was in renal failure with creatinine of 1.9 mg/dL (baseline 0.8 mg/dL). Her parathyroid hormone (PTH) level was 0. A diagnosis of CATS was made. She was treated with intravenous fluids and furosemide and discharged home on hospital day 5 after her calcium and creatinine levels normalized. A triad of hypercalcemia, acute kidney injury and metabolic alkalosis comprises MAS. Traditional MAS was caused by "Sippy diet" (containing milk and alkali) used for the treatment of peptic ulcer disease. Over the decades, the same triad of symptoms occurred in patients using excess calcium and vitamin D, hence changing the name to CAS. A subset of patients at risk for CAS also use thiazide diuretics for hypertension, making them more vulnerable to hypercalcemia and acute kidney injury. In such subset of patients, it is preferable to use the term CATS rather than MAS or CAS.

Comparison of Outcomes After Treatment of Large Vessel Occlusion in a Critical Care Resuscitation Unit or a Neurocritical Care Unit.

BACKGROUND: Mechanical thrombectomy (MT) has become first-line treatment for patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Delay in the interhospital transfer (IHT) of patients from referral hospitals to a comprehensive stroke center is associated with worse outcomes. At our academic tertiary care facility in an urban setting, a neurocritical care and emergency neurology unit (NCCU) receives patients with AIS-LVO from outlying medical facilities. When the NCCU is full, patients with AIS-LVO are initially transferred to a critical care resuscitation unit (CCRU). We were interested in quantifying the numbers of AIS-LVO patients treated in those two units and assessing their outcomes. We hypothesized that the CCRU would facilitate an increase in IHTs and provide care comparable to that delivered by the subspecialty NCCU. METHODS: We conducted a retrospective study of the medical center's prospective stroke registry for adult IHT patients undergoing MT between 01/01/2015 and 12/31/2017. Primary outcome was time from consultation and request for transfer to arrival (Consult-Arrival). Other outcomes of interest were functional independence, defined as 90-day modified Rankin Scale (mRS) score ≤ 2, and 90-day all-cause mortality. Multivariable logistic regression was performed to assess association between clinical factors, mortality, and functional independence. RESULTS: We analyzed the records of 128 IHT patients: 87 (68%) were admitted to the CCRU, and 41 (32%) to the NCCU. The two groups had similar baseline characteristics (age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early Computed Tomography scores [ASPECTS]). The median Consult-Arrival time was shorter for CCRU patients than for the NCCU patients (86 [88‒109] vs 100 [77‒127] [p = 0.031]). The 90-day mortality rates (16 vs 30% [p = 0.052]) and the rates having a mRS score ≤ 2 (31 vs 36% [p = 0.59]) were not statistically different. Multivariable logistic regression showed that each minute of delay in the Consult-Arrival time was associated with 2.3% increase in the likelihood of death (OR 1.023; 95% CI 1.003‒1.04 [p = 0.026]), while high thrombolysis in cerebral infarction score was the only factor that was significantly associated with functional independence at 90 days (OR 2.9; 95% CI 1.4‒6.4 [p = 0.006]). CONCLUSION: The CCRU increased AIS-LVO patients' access to definitive care and reduced their transfer time from outlying medical facilities while achieving outcomes similar to those attained by patients treated in the subspecialty NCCU. We conclude that a resuscitation unit can complement the NCCU to care for patients in the hyperacute phase of AIS-LVO.