Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.

Identifying errors and safety considerations in patients undergoing thrombolysis for acute ischemic stroke.

BACKGROUND & PURPOSE: Alteplase is the standard of care for early pharmacologic thrombolysis after acute ischemic stroke (AIS). Alteplase is also considered a high-alert medication and is fraught with potential for error. We sought to describe the difference in medication error rates in in patients receiving alteplase for acute ischemic stroke from regional hospitals compared to patients receiving alteplase at the Comprehensive Stroke Center. METHODS: This was a retrospective cohort comparison of patients who were greater than 18 years old that received intravenous alteplase for the treatment of AIS from June 2015 to June 2018. Several institution specific databases were utilized to obtain pertinent data. A standardized taxonomy was utilized to classify medication errors. Patients were excluded if they received any fibrinolytic other than alteplase or if alteplase was used for a non-stroke indication. Two cohorts (from regional hospitals or the Comprehensive Stroke Center (CSC)) were compared. RESULTS: A total of 676 patients received alteplase during the study period (34% from the CSC and 66% from regional hospitals). There were 133 (19.8%) errors identified. Ten errors (1.6%) occurred at the CSC and 123 (18.2%) errors occurred at regional hospitals. More patients who had an error with alteplase administration (12.7%) experienced a hemorrhagic conversion compared to those with no error in administration (7.2%, p= 0.04). CONCLUSION: The error rate of alteplase infusion for ischemic stroke is high, particularly in patients from referring centers. Errors may be associated with adverse events. Further education and administration safeguards should be implemented to decrease the risk of medication errors.

Comparison of Low- Versus High-Dose Four-Factor Prothrombin Complex Concentrate (4F-PCC) for Factor Xa Inhibitor-Associated Bleeding: A Retrospective Study.

BACKGROUND: Although andexanet alfa was recently approved as a specific reversal agent for apixaban and rivaroxaban, some providers still elect to administer 4-factor prothrombin complex concentrate (4F-PCC) instead, due to concerns surrounding efficacy, thrombotic risk, administration logistics, availability, and cost. Previous studies have described success with 4F-PCC doses ranging from 25 to 35 U/kg, with some guidelines recommending 50 U/kg. OBJECTIVES: The purpose of this study was to compare hemostasis between patients receiving low- (20-34 U/kg) versus high-dose (35-50 U/kg) 4F-PCC for the urgent reversal of apixaban and rivaroxaban. PATIENTS/METHODS: We performed a retrospective cohort study at a level one trauma center and comprehensive stroke center between January 2015 and December 2018. Main exclusion criteria included patients receiving less than 20 U/kg or if postreversal imaging were unavailable. Outcomes assessed included hemostasis for critical bleeding associated with apixaban or rivaroxaban and postoperative bleeding for reversal for emergent procedures. RESULTS: The low-dose strategy was administered to n = 57 (57.6%) patients at a mean dose of 26.6 U/kg. The high-dose strategy was used in n = 42 (42.4%) patients at a mean dose of 47.6 U/kg. There was no difference in hemostasis by dosing strategy (75.4% vs 78.6%, P = .715) or hospital mortality (19.3% vs 35.7%, P = .067). No difference was found for secondary end points, including thrombotic events (5.3% vs 2.4%, P = .635) and hospital length of stay (11.3 vs 12.5 days, P = .070). CONCLUSIONS: Our comparison addresses a gap in the literature surrounding optimal dosing and supports a similar efficacy profile between dosing low- versus high-dose treatment.

Fever Burden in Patients With Subarachnoid Hemorrhage and the Increased Use of Antibiotics.

BACKGROUND: Fever occurs in the majority of subarachnoid hemorrhage (SAH) patients. Nearly 50% of SAH patients have noninfectious fevers. Data are lacking describing the effects of fever burden in the SAH patient population. METHODS: This was a single-center, retrospective observational cohort study in patients more or equal to 18 years of age with a diagnosis of nontraumatic SAH admitted to an ICU between January 1, 2010 and September 1, 2015. Exclusion criteria were SAH secondary to trauma or admission for more than 48 hours. Temperature measurements, demographic data, and other pertinent information were collected from Day 0 to Day 13. Daily fever burden was calculated for each patient by calculating an area under the curve. RESULTS: A total of 194 subjects were included. The mean study period maximum temperature (Tmax) for all 194 patients was 40.8 ± 0.83°C. The mean overall fever burden for all 194 patients was 89.2 ± 99.59°C h more than 37°C. The overall fever burden peaked on day 5 and declined thereafter. Fever burden, Tmax, and length of stay in the hospital were all significantly associated with receipt of antibiotics. Only Tmax was associated with poor outcome. The 31 patients who had fever but no identified cause of infection received 1000 doses of antibiotics or 32.25 doses per patient. CONCLUSION: Fever is common in SAH patients and is associated with antibiotic use, infection, vasospasm, and poor outcome. Some SAH patients may receive antibiotics unnecessarily for noninfectious fever. Clinicians should consider using site-specific parameters related to infection rather than systemic symptoms such as fever to evaluate infection in SAH patients.

Reversing Direct Oral Anticoagulants in Acute Intracranial Hemorrhage.

Intracerebral hemorrhage is a major source of morbidity and mortality, accounting for 10% of all strokes. Oral anticoagulation therapy, while necessary to prevent thromboembolic complications, increases the risk of intracerebral hemorrhage and can potentially worsen bleeding in cases of acute hemorrhage. Before the introduction of direct oral anticoagulant agents in 2010, warfarin was the only option for oral anticoagulation. These new agents have an improved safety profile compared with warfarin but require different reversal strategies. Anticoagulation reversal in the setting of acute intracerebral hemorrhage is an evolving field. This article covers the most common direct oral anticoagulant medications, various available anticoagulant reversal strategies, and the latest guidelines for anticoagulation reversal in patients with acute intracranial hemorrhage.

Utilization of Pharmacist Responders as a Component of a Multidisciplinary Sepsis Bundle.

BACKGROUND: Sepsis and septic shock remain a significant burden on the US health care system. A multidisciplinary response system (Coordinated Response to Sepsis, CaRTS) that included a pharmacist responder was implemented for patients with newly suspected sepsis. OBJECTIVE: To evaluate the time to appropriate antibiotic administration among patients with the CaRTS intervention compared with historical controls. METHOD: The CaRTS intervention included an electronic order set as well as activation of a multidisciplinary team of pharmacy and nursing personnel to coordinate resuscitation and medication administration. The CaRTS group was compared to historical controls. The primary outcome of the study was the proportion of patients with appropriate antibiotic administration within 1 hour of recognition of sepsis. Secondary outcomes included achievement of mean arterial pressure (MAP) ≥65 mm Hg and central venous pressure (CVP) of 8 to 12 mm Hg within 6 hours. RESULT: The CaRTS intervention was used for 49 patients and 59 historical controls were included for analysis. Patients with the CaRTS intervention had a greater than 20 times higher odds of antibiotic administration within 1 hour compared with controls (odds ratio [OR] 22.4, 95% confidence interval [CI] 7.5-69) and were more likely to have a CVP ≥8 mm Hg at 6 hours (OR 2.4, 95% CI 1.0-5.6) compared with controls. CaRTS patients achieved statistically nonsignificant increases in MAP ≥65 mm Hg (OR 2.2, 95% CI 0.7-7.7). CONCLUSION: Utilization of a multidisciplinary sepsis bundle that included a pharmacist responder improved the proportion of patients receiving appropriate antibiotics within 1 hour of recognition of sepsis compared to historical controls.