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.

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.

Modeling the Clinical Implications of Andexanet Alfa in Factor Xa Inhibitor-Associated Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Andexanet alfa was recently approved as a reversal agent for the factor Xa inhibitors (FXais) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study. METHODS: We simulated potential downstream implications of andexanet alfa across a range of possible hemostatic effects using data from a single center that treats FXai-associated ICH with prothrombin complex concentrate (PCC). We determined baseline probabilities of inadequate hemostasis across patients taking FXai and those not taking FXai via multivariable regression models and then determined the probabilities of unfavorable 3-month outcome (modified Rankin Scale score 4-6) using models comprising established predictors and each patient's calculated probability of inadequate hemostasis. We applied bootstrapping with model parameters from this derivation cohort to simulate a range of hemostatic improvements and corresponding outcomes and then calculated absolute risk reduction (relative to PCC) and projected number needed to treat (NNT) to prevent 1 unfavorable outcome. RESULTS: Training models using real-world patients (n = 603 total, 55 on FXai) had good accuracy in predicting inadequate hemostasis (area under the curve [AUC] 0.78) and unfavorable outcome (AUC 0.78). Inadequate hemostasis was strongly associated with unfavorable outcome (odds ratio 4.5, 95% confidence interval [CI] 2.0-9.9) and occurred in 11.4% of patients taking FXai. Across simulated patients taking FXai comparable to those in A Study in Participants With Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4) study, predicted absolute risk reduction of unfavorable outcome was 4.9% (95% CI 1.3%-7.8%) when the probability of inadequate hemostasis was reduced by 33% and 7.4% (95% CI 2.0%-11.9%) at 50% reduction, translating to projected NNT of 21 (cumulative cost $519,750) and 14 ($346,500), respectively. DISCUSSION: Even optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered. Placebo-controlled randomized trials are needed before its use can definitively be recommended.

Emergency medical services protocols for traumatic brain injury in the United States: A call for standardization.

BACKGROUND: Traumatic brain injury (TBI) with acute elevation in intracranial pressure (ICP) is a neurologic emergency associated with significant morbidity and mortality. In addition to indicated trauma resuscitation, emergency department (ED) management includes empiric administration of hyperosmolar agents, rapid diagnostic imaging, anticoagulation reversal, and early neurosurgical consultation. Despite optimization of in-hospital care, patient outcomes may be worsened by variation in prehospital management. In this study, we evaluate geographic variation between emergency medical services (EMS) protocols for patients with suspected TBI. METHODS: We performed a cross-sectional analysis of statewide EMS protocols in the United States in December 2020 and included all complete protocols published on government websites. Outcome measures were defined to include protocols or orders for the following interventions, given TBI: (1) hyperventilation and end-tidal capnography (EtCO2) goals, (2) administration of hyperosmolar agents, (3) tranexamic acid (TXA) administration for isolated head injury, (4) non-invasive management including head-of-bed elevation, and (5) hemodynamic goals. RESULTS: We identified 32 statewide protocols including Washington, D.C., 4 of which did not include specific guidance for TBI. Of 28 states providing ventilatory guidance, 22/28 (78.6%) recommend hyperventilation, with 17/22 (77.3%) restricting hyperventilation to signs of acute herniation. The remaining 6 states prohibited hyperventilation. Regarding EtCO2 goals among states permitting hyperventilation, 17/22 (77.3%) targeted an EtCO2 of < 35 mmHg, while 5/22 (22.7%) provided no guide EtCO2 for hyperventilation. Rhode Island was the only state identified that included hypertonic saline (3%), and Delaware was the only state that allowed TXA in the setting of isolated TBI with GCS ≤ 12. Only 15/32 (46.9%) identified states recommend head-of-bed elevation. For blood pressure goals, 12/28 (42.9%) of states set minimum systolic blood pressure at 90 mmHg, while 10/28 (35.7%) set other SBP goals. The remaining 6/28 (21.4%) did not provide TBI-specific SBP goals. CONCLUSIONS: There is wide variation among civilian prehospital protocols for traumatic brain injury. Prehospital care within the first "golden hour" may dramatically affect patient outcomes. Neurocritical care providers should be mindful of geographic variation in local protocols when designing and evaluating quality improvement interventions and should aim to standardize prehospital care protocols.

Statewide Emergency Medical Services Protocols for Status Epilepticus Management.

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.