Sunnybrook critical care research coordinators Eily Shaw, Shahin Khodaei and Hannah Rose Rosales. Eily is the research coordinator for the SAVE-ICU trial.
Informally dubbed “Critical Care Central,”
Sunnybrook Health Sciences Centre cares for approximately 2,000 of the most
seriously-injured and sickest patients each year; the highest number in Canada.
It’s this highly-specialized setting within an academic
health sciences centre that lays the foundation for clinical research – the
study of health and illness in people – that drives discovery, innovation and
learning in the field of critical care, at home and around the globe.
According to the Canadian Clinical
Research Network, for the second year in a row, Sunnybrook has enrolled the
highest number of patients in Canada in critical care-related trials funded by the Canadian Institutes of Health Research (CIHR).
Two current Sunnybrook-led clinical trials – on the cusp of discovery – are
expected to produce evidence that will change the way critical care is
practiced, and impact outcomes for critically-ill patients.
The world’s largest clinical trial in critical care: Using antibiotics to prevent hospital-acquired
infections before they happen
Critically-ill patients who receive mechanical
ventilation (assisted breathing) in an intensive care unit (ICU) are
particularly at risk for hospital-acquired infections – these are infections
that can develop while patients are in hospital receiving care, and are a major
cause of illness, sometimes death, and increases to the costs of care.
While the evidence supporting the preventative use of antibiotics is strong,
many health care professionals around the world don’t use this approach, out of
a concern of the effects of antibiotic resistance – when antibiotics are no
longer effective.
Led by Sunnybrook Research Institute in Canada and the U.K., and by The George
Institute in Australia, the SuDDICU study – Selective Decontamination of the Digestive tract in Intensive Care
Unit patients – is a large, randomized controlled trial and
international research collaboration, that was first established in 2009.
The researchers wanted to test:
- whether
using antibiotics to prevent infections increases the number of patients who
get better and go home after being critically unwell, and
- whether
using antibiotics in this way affects patterns of antibiotic resistance – when
antibiotics are no longer effective – in the ICU.
“The preliminary results are not only promising, but also came as a bit of a
surprise,” says Dr. Brian Cuthbertson, international principal investigator of
the trial, critical care physician and senior scientist at Sunnybrook.
“This research aims to give health
care professionals and patients data on the benefits so they can
make informed decisions about providing preventive
antibiotics as part of care.”
Publication of the study results are expected in the
near future – stay tuned to SRI Research News.
The clinical trial ranked #1 out of
hundreds of thousands of Health Canada pandemic study grant applications: Swapping intravenous (IV) sedative for inhaled sedative for patients on a ventilator in
the ICU
This trial is homegrown within Canada (and includes a single U.S. site), but
its potential for global impact is not any less significant. The SAVE-ICU study – SedAting
with Volatile Anesthetics Critically Ill COVID-19 Patients in the Intensive
Care Unit – is a collaborative, multi-hospital,
randomized clinical trial testing:
- whether inhaled volatile
sedatives – a more widely available anesthetic commonly used in operating rooms
– can replace sedative drugs that are typically delivered intravenously (by IV)
for patients in the ICU with respiratory distress requiring ventilation; and
- whether patients recover faster
with this form of sedation.
“In
order to tolerate the uncomfortable procedure of being put on a breathing
machine, patients require sedation or sleep-inducing medications,” explains Dr.
Angela Jerath, lead principal investigator of the study, anesthesiologist, and
a scientist in Evaluative Clinical Sciences at Sunnybrook. “At the beginning of
the COVID-19 pandemic, these drugs were in short supply due to the high number
of patients needing ventilators.”
The investigators will compare the impact that inhaled versus IV sedation has
on outcomes important to patients with respiratory failure, their ICU clinical
teams, and health resource use; this includes ICU and ventilator-free days,
quality of life, delirium and hospital mortality.
Adds Dr. Jerath: “There has been some evidence to suggest that these (inhaled
volatile) drugs may also have properties that reduce lung inflammation, which
may speed up recovery and reduce the time patients spend on a ventilator.”
The investigators are also continuing to look for any elevation in risk between
the two methods of sedation, but there has been no indication to stop in the
last few years, with no adverse events showing.
“As
the inhaled sedative doesn’t have to be filtered through the body like the IV
sedation does, there are benefits for the lungs, liver and kidneys, for cancer
patients, and with no particular concerns over IV sedation seen,” explains Eily
Shaw, the research coordinator on the trial.
“When you turn the dose up/down with an IV drip, you need to wait for the body
to process it first, and there’s also a considerable ‘wash out’ period after
with patients coming off the effects from the sedative days or even weeks
later. It can be a long time before they feel themselves again which can be
confusing and sometimes scary.”
Above, a dose of isoflurane is prepared, as part of the SAVE-ICU trial designed and led by Sunnybrook. The inhaled sedative – known for its use in surgeries – has been tested for use with patients in the intensive care unit, versus traditional sedatives given through an intravenous (IV) line.
Although volatile (inhaled) anesthetics are not new (as a standard of care for
surgeries), “their use still had to be studied in the context of the ICU
because the type of person coming in for surgery is different than the patient
who is ventilated due to respiratory distress in critical care,” says Eily.
At the study start in 2021, it was initially aimed at patients with a COVID
diagnosis, but has since expanded to include any patient in the ICU with any
kind of respiratory distress (lung failure) requiring sedation on a ventilator.
“The goal of this study is to determine if inhaled sedation should be a standard of care in the ICU as well,” says Dr. Jerath. “This can be done differently between
hospitals (with different tiers of care), and would also ease the pressure on IV
sedation stock, in particular during heightened times of need, such as a
pandemic.”
With over 750 research participants over the four-year study period, it will
take another year or two to assess the data. In the meantime, members of the
research team like Eily are left humbled with their own anecdotal personal
observations and sense of what it means:
“I’m always buoyed by how thankful our participants and their families are to be involved in our research. For me,
the human component is what makes the work we do particularly
special. Our team certainly can’t take all the credit but it’s so
massively rewarding to see patients when they get better and they look totally
different at follow ups and are so grateful, we understand the
importance of doing this.”