SAVE-ICU Study

Sedation of Acute care patients with Volatile anEsthetics

Did you know that the way we sedate patients in the ICU can significantly impact their recovery process, cognitive function, and length of stay? SAVE-ICU is a groundbreaking trial set to explore this very question. We would like to share with you why this research could revolutionize patient care in ICUs around the globe.

Traditionally, sedation in the ICU was managed with IV agents like benzodiazepines, propofol, or ketamine. While effective, these agents can linger in the body due to their metabolism by the liver and kidneys — organs which often have impaired function in our ICU patients. This can lead to prolonged sedation times, sedation-associated delirium, delayed liberation from mechanical ventilation, and extended ICU stays.

But what if there was a better way?

Inhaled anesthetic sedatives, such as isoflurane, present a compelling alternative. They're rapidly cleared from the body through exhalation, bypassing the need for liver or kidney metabolism. This not only prevents the accumulation of the drug in the body but also allows for precise control over sedation levels, thanks to the ability to measure exhaled concentrations directly.

Why does this matter for our patients? Inhaled anesthetics have been shown to wake patients up faster after surgery, reduce inflammation in lung injury, and offer bronchodilating properties that improve breathing in patients with conditions like asthma. Plus, they're cost-effective and were crucial during sedation shortages, like those experienced in the COVID-19 pandemic.

So, why haven't we used them in the ICU before? The challenge has been the lack of appropriate delivery and scavenging systems on ICU ventilators. But that's changed with the development of devices like the AnaConDa, which enable the use of inhaled sedation in the ICU setting.

A small but promising study in France showed that patients sedated with inhaled anesthetics had reduced lung inflammation and improved oxygenation, with a trend towards shorter mechanical ventilation and ICU stays. This suggests significant benefits, but larger studies are needed to confirm these findings and guide clinical practice.

SAVE-ICU is a pragmatic multi-centre RCT comparing the effect of sedation with inhaled anesthetics versus intravenous sedatives in mechanically ventilated patients with acute hypoxic respiratory failure on patient (mortality, quality of life) and health system (ICU- and ventilator-free days) outcomes. SAVE-ICU has two prospective cohort studies assessing neurocogntive outcomes (Neuro-SAVE-ICU) and biomarkers (Biomarkers-SAVE-ICU) in patients enrolled in the main RCT.

The purpose of the study is to evaluate whether inhaled volatile sedation can be used effectively in ventilated COVID-19 patients, thereby easing pressure on IV sedation stocks. The study is also evaluating if patients recover faster with this form of sedation.

This work is part of a broader program of research on the use of inhaled anesthetics in the ICU.

For further details, please visit the study pages on the following websites:

SAVE-ICU website: www.saveicu.com
Lawson health research Institute website
Sunnybrook research Institute website
Canadian Critical Care Trials Group website
ClinicalTrials.gov website

Study Interventions

Participants will:

Be randomized to one of the treatment groups, while hospitalized
Receive intravenous or inhaled sedation, administered according to standard sedation practice
Be followed-up with throughout their ICU stay and up to one year after

Intervention / Treatment

Drug: Isoflurane Inhalant Product
Drug: Sevoflurane inhalant product

Inclusion Criteria

Patients who meet ALL of the following:

1. ≥ 18 years of age

2. Mechanically ventilated and expected to remain mechanically ventilated at the end of the next day

3. Receiving IV sedation by infusion or bolus for ≤72 hours to facilitate mechanical ventilation Transferred patients with escalating ventilation needs are eligible for recruitment within ≤72 hours of sedation commenced within the participating trial site that they were transferred to.

Note: Intravenous sedation required to support mechanical ventilation includes use of one or more of the following agents: benzodiazepines, propofol, ketamine, barbiturates, alpha-2 agonist, opioids. Patients receiving intravenous opioids only i.e., fentanyl ≥ 50mcg/hour, hydromorphone ≥ 0.4mg/hour (or bolus q1h) for analgesia and sedation or agitation to assist mechanical ventilation are eligible for inclusion.

4. Proven or suspected (under investigation) COVID-19, or b) COVID-19 negative patients who have a PaO2FiO2 ratio ≤300 measured with arterial blood gas at least once during the 12 hours prior to enrollment.

Exclusion Criteria

Contraindications to sedatives, such as propofol infusion syndrome or malignant hyperthermia;
Known allergy to any of the ingredients or components of the investigational products; sevoflurane or isoflurane;
Suspect or evidence of high intracranial pressure;
Severe brain injury that is likely to lead to sustained very low conscious levels or vegetative state
Severe neuromuscular disorder for example amyotrophic lateral sclerosis, Gullian Barre Syndrome that are the primary cause of needing ICU admission and mechanical ventilation
One-lung ventilation or pneumonectomy;
Ideal estimated tidal volume too low for delivery of inhaled agents. Target (6ml/kg) < 200ml;
Use of inhaled prostacyclin which is contraindicated in the presence of a miniature vaporizer (i.e., Anesthesia Conserving Device). This agent has a high viscosity that leads to poor vaporization of the volatile agent. Note: Other inhaled pulmonary vasodilators such as nitric oxide can be safely administered in the presence of miniature vaporizers. Use of prostacyclin is permissible with an anesthesia machine and MADM;
Known pregnancy
Moribund patient not expected to survive >12 hours

Media

Principal Investigators

Co-Principal Investigator

Sunnybrook

SAVE program

Co-Principal Investigator

London Health Sciences Centre

SAVE program

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