SAVE-ICU STUDY

SEDATION OF ACUTE CARE PATIENTS WITH VOLATILE ANESTHETICS

1. What is this study?

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.

2. Why are we doing it?

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.

3. Who is eligible (enrolment criteria)?

This study will enrol patients from the intensive care units at five participating academic centres:(LHSC, Foothills Medical Centre in Calgary, the Ottawa Hospital, Kingston Health Sciences Centre and the Centre Hospitalier de l'Université de Montréal) beginning in August 2022 for a duration of 3 years. We will approach the substitute decision maker of consecutive patients who are >18, have a consensual plan for WLSM in the intensive care unit, have an indwelling arterial cannula for monitoring arterial pulse pressure, and the attending physicians anticipate death within 24 hours of WLSM. Patients fulfilling criteria for death by neurological criteria or with injuries that anatomically preclude neuromonitoring will be excluded.

4. Study interventions

If a patient agrees to participate in the study, basic information, such as age, gender, diagnosis, and all the standard actions that happen as part of end of life care, such as medicines and medical procedures started and stopped, will be collected from the medical chart and recorded in a database. As well, once the patient's doctor and healthcare team start removing life support, a research coordinator will collect information from the machines that monitor your heart activity, blood pressure, breathing rate and brain activity. If the patient is eligible to be an organ donor they may still participate in this study. Participating in this study will not affect the process of organ donation. This information will be recorded at the central monitoring station and saved electronically and the information will be entered into a database on a password protected, secure website. During this process, you and the healthcare team will not see the information being collected and it will not interfere with your interaction with your family. After the doctor has declared death, we will continue to collect information from the monitors for 30 minutes. This does not change usual practice after death. Your family will be able to be with you throughout the dying process and there will be no restrictions on their activities at the bedside. 

Extra monitors that measure brain activity and function will be used. These include: 

1) a video-electroencephalogram (EEG), an electric tracing measuring brain waves; 

2) transcranial doppler ultrasound test (TCD) which involves placing two probes on the temples of the head which are held in place by a harness to passively examine blood flow in the brain; 

3) evoked potentials, a test used to measure brainstem function; or 

4) event-related potentials, a test designed to assess the possibility of conscious experience.  

Not every participant will have all 4 tests done. The patient will have a maximum of 2 of the 4 tests done depending on the circumstances at the time of testing. The study team will discuss this in detail with the patient or their substitute decision maker (SDM) before performing any tests as part of the study. 

Willing participants will also be asked to complete a form gathering information related to issues of equity, diversity and inclusion. Patients may decline to complete this form.  

5. Resources