Background: Intracranial hemorrhage is a severe and possibly fatal consequence of anticoagulation therapy. Idarucizumab is used in dabigatran-treated patients suffering from intracranial hemorrhage (ICH) to reverse the anticoagulant effect of dabigatran. Systematic review of real-life mortality in these patients is missing. Objectives: A review of all published dabigatran-related ICH cases treated with idarucizumab was performed. We aimed to estimate in-hospital mortality rate in these patients. Method: We searched PubMed and Scopus for all published cases of ICH in idarucizumab/dabigatran-treated patients until May 15, 2021. The assessed outcome was in-hospital mortality. Results: We identified six eligible studies (case series) with 386 patients and 54 single case reports. In-hospital mortality rate was 11.4% in the case series and 9.7% in the case reports. Conclusions: Our analysis provides clinically relevant quantitative data regarding in-hospital mortality in idarucizumab/dabigatran-treated patients with ICH, which is estimated to be 9.7-11.4%.

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y12 inhibitor is an established therapy for a broad spectrum of patients with cardiovascular disease. The ischemic benefit of DAPT is partially offset by its increased bleeding risk, with intracranial hemorrhage (ICH) being the most serious complication. Although uncommon (0.2%-0.3% annually), its cumulative burden can be substantial given the number of patients afflicted by cardiovascular disease worldwide. Patients with a history of stroke or transient ischemic attack harbor a particularly high risk for ICH when treated with DAPT. Prediction rules may assist clinicians when weighing the risk/benefit ratio of prescribing DAPT for patients with stroke/transient ischemic attack in the nonacute, ambulatory setting. Currently, there are no reversal agents that can rapidly and effectively reverse the effect of P2Y12 inhibitors in routine practice, although a reversal agent for ticagrelor is under clinical investigation.

Direct oral anticoagulants are associated with rates of major bleeding which are not negligible, albeit lower than those associated with vitamin K antagonists. No specific reversal agent for factor Xa (FXa) direct inhibitors is currently available for clinical use. A modified activated human FXa decoy protein, andexanet alfa, is being developed that binds FXa direct inhibitors in their active site, thus reversing their anticoagulant effect. The purpose of this article is to review the design, development and clinical trials of andexanet alfa. Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity both in thrombosis animal models, healthy volunteers and patients with acute major bleeding. Andexanet alfa has been studied in double-blind, placebo-controlled phase II and III studies. A preliminary report of the phase III study showed that an effective hemostasis was obtained after andexanet alfa infusion in the majority of the patients with acute major bleeding associated with FXa inhibitors. Additional studies are ongoing and andexanet alfa is expected to be launched in the market in the near future.

Idarucizumab is the first reversal agent approved for the direct thrombin inhibitor dabigatran. The authors summarize the findings from the clinical trial series and describe case reports, post-marketing data, and ongoing studies.

A case is reported in which a 3-days old neonate with a giant ovarian cyst was scheduled for surgery. The patient received a dose of sugammadex to reverse a rocuronium-induced neuromuscular block. A fast and efficient recovery from neuromuscular block was achieved within 90s. No adverse events or other safety concerns were observed. Furthermore, a review of the literature on the use of sugammadex in neonates was performed.

A case is reported in which a 3-days old neonate with a giant ovarian cyst was scheduled for surgery. The patient received a dose of sugammadex to reverse a rocuronium-induced neuromuscular block. A fast and efficient recovery from neuromuscular block was achieved within 90s. No adverse events or other safety concerns were observed. Furthermore, a review of the literature on the use of sugammadex in neonates was performed.

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the \"gold standard\" muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing.