Studies

SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU (SAVE-ICU) is a multicentre open-label, pragmatic, randomized controlled trial (RCT) and a parallel prospective (non-randomized) cohort study that compares the effect of sedation with inhaled volatile anaesthetics (intervention) with intravenous agents (comparator) on a hierarchy of patients and health system outcomes in adult patients with respiratory failure (population). Read more here.

Economic Evaluation Alongside SAVE-ICU (E-SAVE-ICU) is an embedded sub-study of SAVE-ICU RCT that aims to evaluate the comparative cost-effectiveness of inhaled volatile anesthetic-based sedation regimen versus standard/usual care intravenous sedation regimen for critically ill patients. The primary objective of e-SAVE-ICU is to estimate the incremental cost per quality-adjusted life-years (QALY) arising from using inhaled volatile anesthetic (intervention arm) versus IV anesthetic (standard of care arm) during mechanical ventilation of critically ill patients. The secondary objectives are to estimate the incremental cost-effectiveness ratios (ICERs) of cost per life-year gained and cost per mortality averted. This study will use data collected from the SAVE-ICU RCT and link it to data available in Ontario’s provincial healthcare database in 10 centres across Canada.

Neuroimaging, Cognitive and Psychiatric outcomes in the SAVE-ICU trial (Neuro-SAVE-ICU) is prospective cohort sub-study of the SAVE-ICU RCT that aims to compare neuroimaging, cognitive and psychiatric outcomes in critically ill patients receiving inhaled volatile anesthetic-based sedation regimen versus standard/usual care intravenous sedation regimen within SAVE-ICU RCT. Neuro-SAVE-ICU team merges expertise of cognitive neuroscientists, neurologists, neuroradiologists, imaging scientists, intensivists, anesthesiologists and clinical research methodologists and state of the art methods to compare the effects of inhaled vs intravenous sedatives on brain structure and long-term neurocognitive function. The study uses novel state-of-the-art web-based neurocognitive battery, Cambridge Brain Sciences that will enable remote longitudinal assessment of neurocognitive outcomes in participants. Given that psychiatric morbidity can impact neurocognitive outcomes, we will also assess patients for symptoms of depression, anxiety, and post-traumatic stress disorder. In a sub-set of patients, we will also use MRI to compare structural brain changes in participants randomized to inhaled vs. intravenous arms.

Biomarkers-SAVE-ICU is a prospective cohort sub-study of the SAVE-ICU RCT that aims to compare Inflammatory, thrombosis, proteomic, metabolomic, transcriptional, and immunoglobulin profiles of critically ill patients receiving inhaled volatile anesthetic-based sedation regimen versus standard/usual care intravenous sedation regimen within SAVE-ICU RCT. This study builds on the success of Dr Fraser’s team that used state‐of‐the‐art scientific methods, including machine learning, to profile COVID‐19 related pathophysiology and to identify potential therapeutic targets and outcome biomarkers. We will now apply the same strategy to compare the effects of inhaled vs intravenous sedatives on the various biomarkers.

Sedatives-SAVE-ICU is a retrospective cohort study comparing the use analgesic, sedative, and antipsychotic medications among participants of the SAVE-ICU. SAVE-ICU RCT introduced a novel mode of sedation using inhaled agents. These agents can be opioid and sedative sparing. However, adherence to standard of care and novelty of inhaled sedatives may lead to adjunct use of analgesics, IV sedatives and antipsychotics in the intervention arm of the SAVE-ICU trial. Furthermore, given that COVID-19 patients may have higher sedation needs, the use of adjunct analgesics, IV sedatives and antipsychotics in the intervention group maybe more prevalent among COVID-19 participants. The aim of Sedatives-SAVE-ICU retrospective study is to compare the use of use analgesic, sedative, and antipsychotic medications between two arms of the SAVE-ICU trial and provide early indication whether adjunct use of these medications may impact clinical outcomes of the SAVE-ICU trial (ventilator- and ICU- free days). The study’s primary objective is to determine if there is difference in the cumulative dose of opioids between the intervention and control arms of the SAVE-ICU trial. Secondary objectives are to determine if patients in the inhaled sedation arm of the SAVE-ICU trial receive lower cumulative dose of benzodiazepines, non-opioid analgesics, or antipsychotic medications, and whether COVID-19 patients require higher doses of opioids, sedatives, benzodiazepines, non-opioid analgesics, or antipsychotic medications compared to non-COVID patients in both intervention and control arms of the SAVE-ICU trial

Assessing brain network reconfiguration upon changes in sedation (EEG-SAVE-ICU) is a prospective pilot cohort feasibility sub-study of the SAVE-ICU RCT that aims to assess the feasibility of collecting EEG data before, during and after an interruption of sedation (either intravenous or volatile anesthetic) in ventilated critically ill patients for the purpose of calculating the brain network reconfiguration using the Adaptive Reconfiguration Index (ARI) of the patient’s brain networks and other brain networks measures. ARI and other brain network measures (e.g. directed functional connectivity, network hub location) are promising functional markers of brain’s ability to recover awareness when sedation is weaned. This information would be useful to guide complex sedation care, prognosticate conscious recovery levels and even longer-term neurocognitive and functional outcomes. Further, given that there is supportive evidence that volatile agents promote faster return of consciousness, assessing the utility of markers of brain network reconfiguration provides a practical bedside technique that can be used by clinicians in patient care.

Pilot randomized control trials (RCT) showed that inhaled sedative are safeand may shorten duration of ventilation and ICU stay. SAVE-ICU RCT is a large multicentre pragmatic RCT that aims to establish whether sedation with inhaled agents (intervention) compared to IV sedatives (control) improves patient outcomes (mortality, quality of life) and healthcare resource utilization (ICU- and hospital-free days) in patients with COVID and non-COVID ARDS (NCT04415060). While these trials may establish safety and efficacy of inhaled sedatives in critically ill patients, we need to understand the current barriers, facilitators and process that may affect the usability of these sedative in the ICU setting. Survey-SAVE-ICU study will use mixed methods (survey, small focus groups) to survey key stakeholders across Canada to answer this question.

Sedation of critically ill patients with inhaled anesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared to intravenous sedatives. However, the impact of inhaled anesthetics on cognitive and psychiatric outcomes in critically ill patients is unclear. In this systematic review, we summarize existing evidence regarding the effect of sedating critically ill patients with inhaled anesthetics on short (in-hospital) and long (post-hospital discharge) neurocognitive and psychiatric outcomes.

Inhaled volatile anesthetic agents (i.e., sevoflurane, isoflurane) have a long tradition of safe and effective use in operating rooms to provide deep hypnosis appropriate for surgery. In critical care settings, the use of these agents has been mostly limited to ‘rescue’ scenarios in specific medical emergencies that are unresponsive to standard treatments such as severe asthma (status asthmaticus), severe seizures (status epilepticus) and sedation of patients with high and/or difficult sedation needs (e.g. those with burns, chronic pain). Whether inhaled volatile agents should be employed as first line therapy for the above conditions for their combined sedative and therapeutic properties has not been evaluated. Prior to further study and change in practice, evidence summarizing their benefits and limitations needs to be collated. In this systematic review, we summarize the current evidence regarding the efficacy, safety and feasibility of using Inhaled volatile anesthetics in adult and pediatric ICU patient with severe asthma, seizures, and difficult sedation needs.

Inhaled volatile anesthetic agents have been commonly used during the SARS-CoV-2 pandemic providing sedation to critically ill patients with severe form of lung injury known as acute respiratory distress syndrome. Animal models of acute lung injury, sepsis, and shock provide valuable data on cytologic, tissue and organ dysfunction that is not obtainable in human trials. Given the growing interest of employing volatile anesthetics in the critical care setting, there exists a need to summarize the basic science data to inform further human trials and models. The objective of this study is to conduct a systematic review and meta-analysis (depending on feasibility of the data) comparing the effect of inhaled volatile anesthetics to intravenous sedatives on the inflammatory response in animal models of acute respiratory failure, sepsis and shock.

Perioperative and critical care patients have an altered inflammatory response. Volatile agents, whether used in the operating room for anaesthesia or in the intensive care unit for sedation, exert measurable anti-inflammatory and immunomodulatory effects that may translate into beneficial clinical outcomes. In this systematic review we seek to collate existing evidence from perioperative and ICU settings on the anti-inflammatory effects of volatile sedative agents compared with intravenous sedative agents, with the focus on pulmonary and systemic inflammation, and whether these effects correlate with clinically beneficial patient outcomes.