Ibrutinib for Hospitalized Adults With Severe Coronavirus Disease 2019 Infection: Results of the Randomized, Double-Blind, Placebo-Controlled iNSPIRE Study.

Background: Few therapies are approved for hospitalized patients with severe coronavirus disease 2019 (COVID-19). Ibrutinib, a once-daily Bruton tyrosine kinase inhibitor, may mitigate COVID-19-induced lung damage by reducing inflammatory cytokines. The multicenter, randomized, double-blind phase 2 iNSPIRE study evaluated ibrutinib for prevention of respiratory failure in hospitalized patients with severe COVID-19. Methods: Adult patients with severe COVID-19 requiring hospitalization and supplemental oxygen but without respiratory failure were randomized 1:1 (stratified by remdesivir prescription) to ibrutinib 420 mg or placebo once daily for up to 28 days plus standard of care (SOC), including remdesivir and/or dexamethasone. Results: Forty-six patients were randomized to ibrutinib plus SOC (n = 22) or placebo plus SOC (n = 24). The primary endpoint (proportion of patients alive and without respiratory failure through day 28) was not met, with no statistically significant difference adjusting for remdesivir prescription (86% with ibrutinib plus SOC vs 79% with placebo plus SOC; adjusted difference, 5.8% [80% confidence interval, -9.2% to 20.4%]; P = .599). Secondary endpoints also showed no statistically significant improvement with ibrutinib plus SOC. Median treatment duration was 14 days for ibrutinib and placebo. Adverse events were similar with ibrutinib plus SOC vs placebo plus SOC (overall: 55% vs 50%; serious: 18% vs 13%) and were consistent with the known safety profile of ibrutinib. Conclusions: Addition of ibrutinib to SOC did not improve the proportion of patients alive and without respiratory failure through day 28 in hospitalized patients with severe COVID-19. Ibrutinib had a manageable safety profile, with similar safety to placebo. Clinical Trials Registration: NCT04375397.

Developing and Implementing Noninvasive Ventilator Training in Haiti during the COVID-19 Pandemic.

Background: Noninvasive ventilation (NIV) is an important component of respiratory therapy for a range of cardiopulmonary conditions. The World Health Organization recommends NIV use to decrease the use of intensive care unit resources and improve outcomes among patients with respiratory failure during periods of high patient capacity from coronavirus disease (COVID-19). However, healthcare providers in many low- and middle-income countries, including Haiti, do not have experience with NIV. We conducted NIV training and evaluation in Port-au-Prince, Haiti. Objectives: To design and implement a multimodal NIV training program in Haiti that would improve confidence and knowledge of NIV use for respiratory failure. Methods: In January 2021, we conducted a 3-day multimodal NIV training consisting of didactic sessions, team-based learning, and multistation simulation for 36 Haitian healthcare workers. The course included 5 didactic session and 10 problem-based and simulation sessions. All course material was independently created by the study team on the basis of Accreditation Council for Continuing Medical Education-approved content and review of available evidence. All participants completed pre- and post-training knowledge-based examinations and confidence surveys, which used a 5-point Likert scale. Results: A total of 36 participants were included in the training and analysis, mean age was 39.94 years (standard deviation [SD] = 9.45), and participants had an average of 14.32 years (SD = 1.21) of clinical experience. Most trainees (75%, n = 27) were physicians. Other specialties included nursing (19%, n = 7), nurse anesthesia (3%, n = 1), and respiratory therapy (3%, n = 1). Fifty percent (n = 18) of participants stated they had previous experience with NIV. The majority of trainees (77%) had an increase in confidence survey score; the mean confidence survey score increased significantly after training from 2.75 (SD = 0.77) to 3.70 (SD = 0.85) (P < 0.05). The mean knowledge examination score increased by 39.63% (SD = 15.99%) after training, which was also significant (P < 0.001). Conclusion: This multimodal NIV training, which included didactic, simulation, and team-based learning, was feasible and resulted in significant increases in trainee confidence and knowledge with NIV. This curriculum has the potential to provide NIV training to numerous low- and middle-income countries as they manage the ongoing COVID-19 pandemic and rising burden of noncommunicable disease. Further research is necessary to ensure the sustainability of these improvements and adaptability to other low- and middle-income settings.

Management of Acute Ischemic Stroke-Specific Focus on Anesthetic Management for Mechanical Thrombectomy.

Acute ischemic stroke is a neurological emergency with a high likelihood of morbidity, mortality, and long-term disability. Modern stroke care involves multidisciplinary management by neurologists, radiologists, neurosurgeons, and anesthesiologists. Current American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend thrombolytic therapy with intravenous (IV) alteplase within the first 3-4.5 hours of initial stroke symptoms and endovascular mechanical thrombectomy within the first 16-24 hours depending on specific inclusion criteria. The anesthesia and critical care provider may become involved for airway management due to worsening neurologic status or to enable computerized tomography (CT) or magnetic resonance imaging (MRI) scanning, to facilitate mechanical thrombectomy, or to manage critical care of stroke patients. Existing data are unclear whether the mechanical thrombectomy procedure is best performed under general anesthesia or sedation. Retrospective cohort trials favor sedation over general anesthesia, but recent randomized controlled trials (RCT) neither suggest superiority nor inferiority of sedation over general anesthesia. Regardless of anesthesia type, a critical element of intraprocedural stroke care is tight blood pressure management. At different phases of stroke care, different blood pressure targets are recommended. This narrative review will focus on the anesthesia and critical care providers' roles in the management of both perioperative stroke and acute ischemic stroke with a focus on anesthetic management for mechanical thrombectomy.

Anesthesia for Patients with Extensive Trauma.

Trauma anesthesiology is a unique and growing subspecialty. With the growing number of adult and pediatric trauma centers in the United States, a thorough understanding of the early management of severely injured patients with trauma is an important aspect of anesthesia. Trauma anesthesiology requires the ability to adapt to different work environments, including the trauma bay, the operating room, and even the intensive care unit, where a patient room may require conversion to an operating suite for emergencies. This article provides a review of the anesthetic management for patients with extensive trauma, focusing on physiology, pharmacology, and bedside management.