Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Prospective validation of the ICH Score for 12-month functional outcome.

BACKGROUND: The ICH Score is a commonly used clinical grading scale for outcome after acute intracerebral hemorrhage (ICH) and has been validated for 30-day mortality, but not long-term functional outcome. The goals of this study were to assess whether the ICH Score accurately stratifies patients with regard to 12-month functional outcome and to further delineate the pace of recovery of patients during the first year post-ICH. METHODS: We performed a prospective observational cohort study of all patients with acute ICH admitted to the emergency departments of San Francisco General Hospital and UCSF Medical Center from June 1, 2001, through May 31, 2004. Components of the ICH Score (admission Glasgow Coma Scale score, initial hematoma volume, presence of intraventricular hemorrhage, infratentorial ICH origin, and age) were recorded along with other clinical characteristics. Patients were then assessed with the modified Rankin Scale (mRS) at hospital discharge, 30 days, and 3, 6, and 12 months post-ICH. RESULTS: Of 243 patients, 95 (39%) died during initial acute hospitalization. The ICH Score accurately stratified patients with regard to 12-month functional outcome for various dichotomous cutpoints along the mRS (p < 0.05). Many patients continued to improve across the first year, with a small number of patients becoming disabled or dying due to late events unrelated to the initial ICH. CONCLUSIONS: The ICH Score is a valid clinical grading scale for long-term functional outcome after acute intracerebral hemorrhage (ICH). Many ICH patients improve after hospital discharge and this improvement may continue even after 6 months post-ICH.

Continuous monitoring of the microcirculation in neurocritical care: an update on brain tissue oxygenation.

PURPOSE OF REVIEW: This article summarizes recent clinical and experimental studies of parenchymal brain tissue oxygen monitoring and considers future directions for its use in neurocritical care. RECENT FINDINGS: Recent reports have focused on the relationship between brain tissue oxygen tension (PbrO2) and other physiologic parameters such as mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and fraction of inspired oxygen. PbrO2 appears to reflect both regional and systemic oxygen concentrations as well as microvascular perfusion through natural tissue gradients. Defining an absolute critically low PbrO2 threshold has been challenging, but levels below 14 mmHg may have a pathophysiologic basis. Newer studies have examined dynamic changes in PbrO2 during oxygen reactivity testing and during augmentation of cerebral perfusion pressure. PbrO2 monitoring has now been described in a wide range of neurocritical care conditions including head trauma, subarachnoid hemorrhage, nontraumatic intracerebral hemorrhage, brain death, and brain tumor resection. SUMMARY: The use of brain tissue oxygen monitoring is maturing as a tool to detect and treat secondary brain injury. PbrO2 measurements can provide continuous quantitative data about injury pathophysiology and severity that may help optimize neurointensive care management. Prospective trials of PbrO2 guided treatment protocols are now needed to demonstrate impact on clinical outcomes.