Impact of intracranial atherosclerosis burden on vasospasm risk and outcomes in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is a well-known complication after aneurysmal subarachnoid hemorrhage (aSAH) and occurs more commonly in younger patients. We hypothesized that intracranial atherosclerosis, which is seen predominantly in older patients, affects vasospasm risk. We sought to determine association between intracranial atherosclerosis burden with vasospasm and outcomes in aSAH. METHODS: We retrospectively reviewed a cohort of consecutive patients with aSAH admitted to a Comprehensive Stroke Center between 2016 and 2023. Intracranial atherosclerosis burden was quantified by using modified Woodcock (MW) score on CT angiograms. Vasospasm was defined based on transcranial Doppler (TCD) criteria. Poor outcome was defined as 3-month modified Rankin Scale 3-6. RESULTS: We reviewed 392 patients and included 302 (mean age 56.8 years [SD 13.3], 65 % female and 70 % white) in the final analysis. MW scores were measured with excellent intra-rater and inter-rater reliability (Cohen's kappa coefficient 0.9 and 0.83 respectively) ranging from 0 to 3 (mean 0.59, SD 0.83) with higher scores in older patients (beta coefficient 0.019, 95 % CI 0.009-0.028; p < 0.001). Higher MW calcification score was associated with lower risk of vasospasm (OR 0.52 per point increase, 95 % CI 0.36-0.78; p = 0.001). There was an inverse correlation between MW scores and severity of vasospasm (beta coefficient -0.29, 95 % CI -0.48, -0.1; p = 0.003). However, MW score was not independently associated with poor functional outcome (p = 0.62). CONCLUSIONS: Intracranial atherosclerosis is a potential mechanism for lower TCD-based vasospasm in older patients with aSAH; however, it may not impact functional outcomes. Larger prospective studies are needed to confirm our findings.

Comparison of Risk Factors for Early Seizures Between Angiogram-Negative and Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Early-onset seizures are common in aneurysmal subarachnoid hemorrhage (aSAH), with risk factors that have been explored. However, early-onset seizures in patients with angiogram-negative nonperimesencephalic SAH (an-SAH) are less understood. We sought to compare the incidence and risk factors of early-onset seizures between these groups. METHODS: We conducted a retrospective study of a cohort of consecutive patients admitted to an academic center between July 2016 and July 2023. Patients were categorized into aSAH or an-SAH based on imaging findings. Clinical data and electroencephalogram findings were retrieved and analyzed. Multivariable logistic regression analysis was used to determine risk factors for clinical or electrographic seizures, as well as other epileptic features. RESULTS: We included 473 patients (63% female) in the final analysis, of whom 79 had an-SAH and 394 had aSAH. Patients with an-SAH were older (mean age 61.9 years [standard deviation 15.9] vs. 56.7 [standard deviation 13.4]; p = 0.02). The rate of clinical or electrographic seizures was similar between the two groups (13% in aSAH vs. 11% in an-SAH; p = 0.62). Highly epileptic features (electrographic seizures, ictal-interictal continuum, and periodic epileptic discharges) occurred more frequently in the aSAH group compared with the an-SAH group, although this difference was not significant (15% vs. 8%; p = 0.09). Risk factors for seizures in aSAH were Hunt and Hess grade (odds ratio [OR] 1.25 per grade increase, 95% confidence interval [CI] 1.05-1.49; p = 0.011), modified Fisher score (OR 1.64 per point increase, 95% CI 1.25-2.15; p < 0.001), cerebral infarct (OR 3.64, 95% CI 2.13-6.23; p < 0.001), and intracerebral hemorrhage (OR 10, 95% CI 1.35-76.9; p = 0.017). However, none of these factors were associated with seizures in an-SAH. CONCLUSIONS: Early-onset seizures occur at similar rates in patients with an-SAH and aSAH. However, seizure risk factors appear to differ between these groups. Larger prospective studies are needed to identify predictors of seizures in patients with an-SAH.

Prevalence of clinical electroencephalography findings in stroke patients with delirium.

OBJECTIVE: Delirium is an acute cognitive disorder associated with multiple electroencephalographic (EEG) abnormalities in non-neurological patients, though specific EEG characteristics in patients with stroke remain unclear. We aimed to compare the prevalence of EEG abnormalities in stroke patients during delirium episodes with periods that did not correspond to delirium. METHODS: We retrospectively analyzed clinical EEG reports for stroke patients who received daily delirium assessments as part of a prospective study. We compared the prevalence of EEG features corresponding to patient-days with vs. without delirium, including focal and generalized slowing, and focal and generalized epileptiform abnormalities (EAs). RESULTS: Among 58 patients who received EEGs, there were 192 days of both EEG and delirium monitoring (88% [n = 169] corresponding to delirium). Generalized slowing was significantly more prevalent on days with vs. without delirium (96% vs. 57%, p = 0.03), as were bilateral or generalized EAs (38% vs. 13%, p = 0.03). In contrast, focal slowing (53% vs. 74%, p = 0.11) and focal EAs were less prevalent on days with delirium (38% vs. 48%, p = 0.37), though these differences were not statistically significant. CONCLUSIONS: We found a higher prevalence of generalized but not focal EEG abnormalities in stroke patients with delirium. SIGNIFICANCE: These findings may reinforce the diffuse nature of delirium-associated encephalopathy, even in patients with discrete structural lesions.

Predictors of hospital length of stay and long-term care facility placement in aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently associated with complications, extended hospital length of stay (LOS) and high health care related costs. We sought to determine predictors for hospital LOS and discharge disposition to a long-term care facility (LTCF) in aSAH patients. Methods: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic referral center from 2016 to 2021. Multiple linear regression was performed to identify predictors for hospital LOS. We then created a 10-point scoring system to predict discharge disposition to a LTCF. Results: In a cohort of 318 patients with confirmed aSAH, mean age was 57 years (SD 13.7), 61% were female and 70% were white. Hospital LOS was longer for survivors (median 19 days, IQR 14-25) than for non-survivors (median 5 days, IQR 2-8; p < 0.001). Main predictors for longer LOS for this cohort were ventriculoperitoneal shunt (VPS) requirement (p < 0.001), delayed cerebral ischemia (p = 0.026), and pneumonia (p = 0.014). The strongest predictor for LTCF disposition was age older than 60 years (OR 1.14, 95% CI 1.07-1.21; p < 0.001). LTCF score had high accuracy in predicting discharge disposition to a LTCF (area under the curve [AUC] 0.83; 95% CI 0.75-0.91). Forty-one percent of patients who were discharged to a LTCF had significant functional recovery at 3 months post-discharge. Conclusions: VPS requirement and aSAH related complications were associated with longer hospital LOS compared to other factors. LTCF score has high accuracy in predicting discharge disposition to a LTCF.

Comparison of the Effects of Blood Pressure Parameters on Rebleeding and Outcomes in Unsecured Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated systolic blood pressure (SBP) has been linked to preprocedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study seeks to compare the effects of SBP and mean arterial pressure (MAP) on rebleeding and functional outcomes in aSAH patients. METHODS: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center in 2016-2023. Binary regression analysis was used to determine the association between BP parameters and outcomes including rebleeding and poor outcome defined as modified Rankin Scale 4-6 at 3 months postdischarge. RESULTS: The cohort included 324 patients (mean age 57 years [standard deviation 13.4], 61% female). Symptomatic rebleeding occurred in 34 patients (11%). Higher BP measurements were recorded in patients with rebleeding and poor outcome, however, only MAP met statistical significance for rebleeding (odds ratio {OR} 1.02 for 1 mmHg increase in MAP, 95% confidence interval {CI}: 1.001-1.03, P = 0.043; OR 1 per 1 mmHg increase in SBP, 95% CI 0.99-1.01; P = 0.06)) and for poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.002-1.025, P = 0.025; OR 1 for 1 mmHg increase in SBP, 95% CI: 0.99-1.02, P = 0.23) independent of other predictors. CONCLUSIONS: MAP may appear to be slightly better correlated with rebleeding and poor outcomes in unsecured aSAH compared to SBP. Larger prospective studies are needed to identify and mitigate risk factors for rebleeding and poor outcome in aSAH patients.

A reassessment of hemoglobin and hematoma expansion in intracerebral hemorrhage.

BACKGROUND: In patients with spontaneous intracerebral hemorrhage (ICH), prior studies identified an increased risk of hematoma expansion (HE) in those with lower admission hemoglobin (Hgb) levels. We aimed to reproduce these findings in an independent cohort. METHODS: We conducted a cohort study of patients admitted to a Comprehensive Stroke Center for acute ICH within 24 hours of onset. Admission laboratory and CT imaging data on ICH characteristics including HE (defined as >33% or >6 mL), and 3-month outcomes were collected. We compared laboratory data between patients with and without HE and used multivariable logistic regression to determine associations between Hgb, HE, and unfavorable 3-month outcomes (modified Rankin Scale 4-6) while adjusting for confounders including anticoagulant use, and laboratory markers of coagulopathy. RESULTS: Among 345 patients in our cohort (mean [SD] age 72.9 [13.7], 49% male), 71 (21%) had HE. Patients with HE had similar Hgb versus those without HE (mean [SD] 13.1 [1.8] g/dl vs. 13.1 [1.9] g/dl, p=0.92). In fully adjusted multivariable models, Hgb was not associated with HE (OR per 1g/dl 1.01, 95% CI 0.86 -1.17, p = 0.94), however higher admission Hgb levels were associated with lower odds of unfavorable 3-month outcome (OR 0.83 per 1 g/dl Hgb, 95% CI 0.72-0.96, p=0.01). CONCLUSION: We did not confirm a previously reported association between admission Hgb and HE in patients with ICH, although Hgb and HE were both associated with poor outcome. These findings suggest that the association between Hgb and poor outcome is mediated by other factors.

Radiographic predictors of aneurysmal etiology in patients with aneurysmal pattern subarachnoid hemorrhage.

OBJECTIVE: Spontaneous angiogram-negative nonperimesencephalic subarachnoid hemorrhage (an-NPSAH) can represent a diagnostic and management dilemma. The authors sought to determine radiographic predictors of aneurysmal etiology based on admission noncontrast head CT scans. METHODS: The authors performed a retrospective cohort study of prospectively collected data from consecutive patients who were admitted for spontaneous subarachnoid hemorrhage (SAH) with suspected aneurysmal etiology to an academic center from 2016 to 2021. They compared blood thickness in the basal cisterns and sylvian fissures and modified Graeb scores on admission head CT scans between the two groups and subsequently developed a predictive model to identify aneurysmal etiology. RESULTS: Of 259 included patients (mean age 56 years [SD 12.7 years]; 55% female), 209 had aneurysmal SAH (aSAH) and 50 had an-NPSAH. The median modified Graeb scores were similar for aSAH and an-NPSAH (6 [IQR 2-10] vs 3.5 [IQR 0-8.5], p = 0.33). The mean blood thickness was greater in the sylvian fissure (p = 0.010) and interhemispheric cisterns (p = 0.002), and there was a greater median degree of extension of blood in the sylvian fissures (p = 0.001) in aSAH than in an-NPSAH patients, but the mean blood thickness was less in the prepontine cistern (p = 0.014). The authors' scoring model was constructed based on differences in radiographic features. Receiver operating characteristic curve analysis showed acceptable accuracy in predicting aneurysmal etiology (area under the curve 0.71, 95% CI 0.62-0.79). CONCLUSIONS: There are differences in radiographic features on admission head CT between an-NPSAH and aSAH patients. The authors' proposed risk stratification model may be considered for further development and use in clinical practice in the future.

Highs and Lows: Dysnatremia and Patient Outcomes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Disturbances in serum sodium concentration (dysnatremia) are common following aneurysmal subarachnoid hemorrhage (aSAH), but its direct impact on outcomes is not well understood. This study aimed to examine the association between dysnatremia following aSAH and patient outcomes. METHODS: A retrospective cohort study of consecutive patients with aSAH who were admitted to an academic referral center between 2015 and 2021 was performed. Multivariate logistic regression was used to test the association of dysnatremia and outcomes including modified Rankin Scale score at 3 months after discharge and vasospasm. Multiple linear regression was used to test the association of hospital length of stay and dysnatremia. RESULTS: We included 320 patients with confirmed aneurysmal etiology (mean [SD] age = 57.8 [14.3] years; 61% female; 70% White). No independent associations were found between hyponatremia or hypernatremia and functional outcome or vasospasm. However, hospital length of stay was longer in patients with hypernatremia (7 more days; 95% confidence interval = 4.4-9.6, P < 0.001) independent of age, Hunt and Hess grade, modified Fisher score, delayed cerebral ischemia, and other hospital complications. CONCLUSIONS: Although dysnatremia may not directly impact functional outcome or vasospasm risk, hypernatremia may prolong hospital length of stay. Judicious use of hypertonic saline solutions and avoidance of unnecessary dysnatremia in patients with aSAH should be considered.

Cisternal Score: A Radiographic Score to Predict Ventriculoperitoneal Shunt Requirement in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Persistent hydrocephalus requiring a ventriculoperitoneal shunt (VPS) can complicate the management of aneurysmal subarachnoid hemorrhage (aSAH). Identification of high-risk patients may guide external ventricular drain management. OBJECTIVE: To identify early radiographic predictors for persistent hydrocephalus requiring VPS placement. METHODS: In a 2-center retrospective study, we compared radiographic features on admission noncontrast head computed tomography scans of patients with aSAH requiring a VPS to those who did not, at 2 referral academic centers from 2016 through 2021. We quantified blood clot thickness in the basal cisterns including interpeduncular, ambient, crural, prepontine, interhemispheric cisterns, and bilateral Sylvian fissures. We then created the cisternal score (CISCO) using features that were significantly different between groups. RESULTS: We included 229 survivors (mean age 55.6 years [SD 13.1]; 63% female) of whom 50 (22%) required VPS. CISCO was greater in patients who required a VPS than those who did not (median 4, IQR 3-6 vs 2, IQR 1-4; P < .001). Higher CISCO was associated with higher odds of developing persistent hydrocephalus with VPS requirement (odds ratio 1.6 per point increase, 95% CI 1.34-1.9; P < .001), independent of age, Hunt and Hess grades, and modified GRAEB scores. CISCO had higher accuracy in predicting VPS requirement (area under the curve 0.75, 95% CI 0.68-0.82) compared with other predictors present on admission. CONCLUSION: Cisternal blood clot quantification on admission noncontrast head computed tomography scan is feasible and can be used in predicting persistent hydrocephalus with VPS requirement in patients with aSAH. Future prospective studies are recommended to further validate this tool.

Trends in Venous Thromboembolism Readmission Rates after Ischemic Stroke and Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS) hospitalization. METHODS: Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines. RESULTS: Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4-6 weeks (P<0.001). In AIS, cancer, obesity, higher National Institutes of Health Stroke Scale (NIHSS) score, longer hospital stay, home or rehabilitation disposition, and absence of atrial fibrillation were associated with VTE readmission. In ICH, longer hospital stay and rehabilitation disposition were associated with VTE readmission. The VTE rate was higher in ICH compared to AIS (adjusted hazard ratio 2.86, 95% confidence interval 1.93-4.25, P<0.001). CONCLUSIONS: After stroke, VTE readmission risk is highest within the first 4-6 weeks and nearly three-fold higher after ICH vs. AIS. VTE risk is linked to decreased mobility and hypercoagulability. Studies are needed to test short-term VTE prophylaxis beyond hospitalization in high-risk patients.

Association of hemoglobin trend and outcomes in aneurysmal subarachnoid hemorrhage: A single center cohort study.

BACKGROUND: Anemia has been linked to delayed cerebral ischemia (DCI) and worse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the association of hemoglobin (Hb) trend and outcomes is not well studied. We investigated predictors of Hb trend and its association with outcomes in patients with aSAH. Our hypothesis was that a negative Hb trend is associated with poorer outcomes independent of Hb values. METHODS: We conducted a retrospective study of a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center (2016-2021). We tested the association of Hb trend and values with measures including DCI and poor functional outcome defined as modified Rankin scale 4-6 at 3 months after discharge. Multiple linear regression analysis was used to identify factors associated with Hb difference from admission to discharge. RESULTS: We included 310 patients with confirmed aneurysmal etiology (mean age 57 years, SD13.6; 62 % female). Greater Hb decrement from admission to discharge was independently associated with higher likelihood of both DCI (OR 1.28 per 1 g/dl decrease in Hb, 95 % CI 1.08-1.47; p = 0.003) and poor functional outcome (OR 1.27 per 1 g/dl decrease in Hb, 1.03-1.53; p = 0.026) independent of any absolute Hb values. Predictors of Hb decrement from admission to discharge were hospital length of stay, Hunt and Hess grades, female sex and age. CONCLUSION: Greater Hb decrement can be associated with higher likelihood of DCI and poor functional outcome in aSAH. More evidence is needed to use Hb trend to guide transfusion threshold in aSAH patients.

A quantitative model to differentiate nonaneurysmal perimesencephalic subarachnoid hemorrhage from aneurysmal etiology.

OBJECTIVE: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (pmSAH) is considered to have a lower-risk pattern than other types of subarachnoid hemorrhage (SAH). However, a minority of patients with pmSAH may harbor a causative posterior circulation aneurysm. To exclude this possibility, many institutions pursue exhaustive imaging. In this study the authors aimed to develop a novel predictive model based on initial noncontrast head CT (NCHCT) features to differentiate pmSAH from aneurysmal causes. METHODS: The authors retrospectively reviewed patients admitted to an academic center for treatment of a suspected aneurysmal SAH (aSAH) during the period from 2016 to 2021. Patients with a final diagnosis of pmSAH or posterior circulation aSAH were included. Using NCHCT, the thickness (continuous variable) and location of blood in basal cisterns and sylvian fissures (categorical variables) were compared between groups. A scoring system was created using features that were significantly different between groups. Receiver operating characteristic curve analysis was used to measure the accuracy of this model in predicting aneurysmal etiology. A separate patient cohort was used for external validation of this model. RESULTS: Of 420 SAH cases, 48 patients with pmSAH and 37 with posterior circulation aSAH were identified. Blood thickness measurements in the crural and ambient cisterns and interhemispheric and sylvian fissures and degree of extension into the sylvian fissure were all significantly different between groups (all p < 0.001). The authors developed a 10-point scoring model to predict aneurysmal causes with high accuracy (area under the curve [AUC] 0.99; 95% CI 0.98-1.00; OR per point increase 10; 95% CI 2.18-46.4). External validation resulted in persistently high accuracy (AUC 0.97; 95% CI 0.92-1.00) of this model. CONCLUSIONS: A risk stratification score using initial blood clot burden may accurately differentiate between aneurysmal and nonaneurysmal pmSAH. Larger prospective studies are encouraged to further validate this quantitative tool.

Association of asymptomatic cerebral vasospasm with outcomes in survivors of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm (cVSP) is a common complication in aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP is poorly understood. We sought to determine the association of asymptomatic cVSP with functional outcome and hospital length of stay (LOS). METHODS: We performed a retrospective study of a prospectively collected cohort of patients with aSAH who survived hospitalization at an academic center between 2016 and 2021. We defined cVSP based on transcranial Doppler criteria. Multivariate logistic and multiple linear regression analyses were used to determine the association of asymptomatic cVSP with poor functional outcome (defined as modified Rankin scale 3-6 at 3 months after discharge) and hospital length of stay (LOS). RESULTS: The cohort consisted of 201 aSAH patients with a mean age 54.9 years (SD 13.6) and 60% were female. One hundred nine patients (54%) experienced cVSP, of whom 43 patients (39%) were asymptomatic. Patients with asymptomatic cVSP were younger (mean 50.5 years [SD 10.6] vs 61 years [SD12.5]; p < 0.001) and had longer ICU LOS (median 13 days [IQR12-20] vs median 12 days [IQR9-15], p = 0.018) compared to those without cVSP. However, after adjusting with other variables asymptomatic cVSP was not associated with longer ICU or hospital LOS. Asymptomatic cVSP was not associated with poor outcome either (p = 0.14). CONCLUSION: Asymptomatic cVSP, which was more common in younger patients, was neither associated with poor functional outcome nor hospital LOS.  Larger prospective studies are needed to assess the significance of asymptomatic cVSP on long-term outcomes.

Association of pre-admission antihypertensive agents and outcomes in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients. METHODS: We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD). RESULTS: The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome. CONCLUSION: Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Risk Factors for Opioid Utilization in Patients with Intracerebral Hemorrhage.

BACKGROUND: Headache is a common presenting symptom of intracerebral hemorrhage (ICH) and often necessitates treatment with opioid medications. However, opioid prescribing patterns in patients with ICH are not well described. We aimed to characterize the prevalence and risk factors for short and longer-term opioid use in patients with ICH. METHODS: We conducted a retrospective cohort study using data from a single-center registry of patients with nontraumatic ICH. This registry included data on demographics, ICH-related characteristics, and premorbid, inpatient, and postdischarge medications. After excluding patients who died or received end-of-life care, we used multivariable regression models adjusted for premorbid opioid use to determine demographic and ICH-related risk factors for inpatient and postdischarge opioid use. RESULTS: Of 468 patients with ICH in our cohort, 15% (n = 70) had premorbid opioid use, 53% (n = 248) received opioids during hospitalization, and 12% (n = 53) were prescribed opioids at discharge. The most commonly used opioids during hospitalization were fentanyl (38%), oxycodone (30%), morphine (26%), and hydromorphone (7%). Patients who received opioids during hospitalization were younger (univariate: median [interquartile range] 64 [53.5-74] vs. 76 [67-83] years, p < 0.001; multivariable: odds ratio [OR] 0.96 per year, 95% confidence interval [CI] 0.94-0.98) and had larger ICH volumes (univariate: median [interquartile range] 10.1 [2.1-28.6] vs. 2.7 [0.8-9.9] cm3, p < 0.001; multivariable: OR 1.05 per cm3, 95% CI 1.03-1.08) than those who did not receive opioids. All patients who had external ventricular drain placement and craniotomy/craniectomy received inpatient opioids. Additional risk factors for increased inpatient opioid use included infratentorial ICH location (OR 4.8, 95% CI 2.3-10.0), presence of intraventricular hemorrhage (OR 3.9, 95% CI 2.2-7.0), underlying vascular lesions (OR 3.0, 95% CI 1.1-8.1), and other secondary ICH etiologies (OR 7.5, 95% CI 1.7-32.8). Vascular lesions (OR 4.0, 95% CI 1.3-12.5), malignancy (OR 5.0, 95% CI 1.5-16.4), vasculopathy (OR 10.0, 95% CI 1.8-54.2), and other secondary etiologies (OR 7.2, 95% CI 1.8-29.9) were also risk factors for increased opioid prescriptions at discharge. Among patients who received opioid prescriptions at discharge, 43% (23 of 53) continued to refill their prescriptions at 3 months post discharge. CONCLUSIONS: Inpatient opioid use in patients with ICH is common, with some risk factors that may be mechanistically connected to primary headache pathophysiology. However, the lower frequency of opioid prescriptions at discharge suggests that inpatient opioid use does not necessarily lead to a high rate of long-term opioid dependence in patients with ICH.

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.

Impact of Delirium on Outcomes After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site. METHODS: We performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4-6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site. RESULTS: Of 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3-16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8-5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17-0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7-5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2-4.3]). CONCLUSIONS: Acute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.

Safety of Modified Nimodipine Dosing in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Nimodipine improves outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the impact of alternative dosing strategies on outcome remains unclear. METHODS: We performed a retrospective cohort study of consecutive patients admitted with aSAH to an academic referral center from 2016 to 2019. Patients with a confirmed aneurysm cause who received nimodipine were included; patients who died or had withdrawal of life-sustaining treatment within 24 hours of admission were excluded. Univariable and multivariable modified Poisson regression models were used to identify predictors of using modified nimodipine dosing (30 mg every 2 hours) versus standard dosing (60 mg every 4 hours). Inverse probability weighted and modified Poisson regression models were used to estimate adjusted risk ratios (RRs) for outcome measures, with poor outcome defined as modified Rankin Scale score 4-6 at 3 months. RESULTS: We identified 175 patients with aSAH who met eligibility criteria (mean [SD] age = 57 [13.2] years, 62% female, 73% White); 49% (n = 86) received modified nimodipine dosing. A modified dose was used more frequently in women (RR 2.08, 95% confidence interval [CI] 1.11-3.89, P = 0.02), patients with vasospasm (RR 3.47, 95% CI 1.84-6.51, P < 0.001), and patients who required vasopressors (RR 1.73, 95% CI 1.3-2.32, P < 0.001). Modified dosing was not associated with poor functional outcome (inverse probability weighted RR 1.1, 95% CI 0.8-1.4, P = 0.65). CONCLUSIONS: Modified dosing of nimodipine is well tolerated and may not be associated with worse functional outcome. Prospective studies are needed to better assess the relationship between nimodipine dosing and outcomes in patients with aSAH.

Gender Disparities in Stroke Code Activation in Patients with Intracerebral Hemorrhage.

OBJECTIVES: Routine implementation of protocol-driven stroke "codes" results in timelier and more effective acute stroke management. However, it is unclear if patient demographics contribute to disparities in stroke code activation. We aimed to explore these demographic factors in a retrospective cohort study of patients with intracerebral hemorrhage (ICH). MATERIALS AND METHODS: We identified consecutive patients with non-traumatic ICH who presented directly to our Comprehensive Stroke Center over 2 years and collected data on demographics, clinical features, and stroke code activation. We used multivariable logistic regression to examine differences in stroke code activation based on patient demographics while adjusting for initial clinical features (NIH Stroke Scale, FAST [facial drooping, arm weakness, speech difficulties] vs. non-FAST symptoms, time from last-known-well [LKW], and systolic blood pressure [SBP]). RESULTS: Among 265 patients, 68% (n=179) had a stroke code activation. Stroke codes occurred less frequently in women (62%) than men (72%) and in non-white (57%) vs. white patients (70%). Non-stroke code patients were less likely to have FAST symptoms (37% vs. 87%) and had lower initial SBP (mean±SD 159.3±34.2 vs. 176.0±31.9 mmHg) than stroke code patients. In our primary multivariable models, neither age nor race were associated with stroke code activation. However, women were significantly less likely to have stroke codes than men (OR 0.49 [95% CI 0.24-0.98]), as were non-FAST symptoms (OR 0.11 [95% CI 0.05-0.22]). CONCLUSIONS: Our data suggest gender disparities in emergency stroke care that should prompt further investigations into potential systemic biases. Increased awareness of atypical stroke symptoms is also warranted.