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LONDON, ON – Hospital researchers from Lawson Health Research Institute have published a recent study that assessed the use of a specialized treatment for chronic pain and its impact on health care use and opioid prescribing.   

Paravertebral blocks (PVBs) belong to a broader group of procedures called “nerve blocks.” A recent Toronto Star report noted that OHIP has been billed $420 million for nerve block procedures since 2011. PVBs involve injecting medication around the nerves where they exit the bones of the spine, at different locations depending on the patient and the chronic pain they are experiencing.  

The regular use of these procedures has been questioned by health care providers due to the high cost and limited evidence of their benefit in reducing chronic pain. While the effectiveness of PVBs has been examined in trauma, cancer pain and regional anesthesia during surgery, they have not been evaluated for use in chronic pain despite widespread use in Ontario.  

It is estimated that one in five Canadians live with chronic pain. Pain that persists can affect all aspects of someone’s life and health, particularly when it is not being managed.  

This new study from London researchers found that 66,310 patients had a PVB between July 2013 and March 2018, and 47,723 patients were included in the study. In the year after a patient’s first PVB, there was a significant increase in the number of physician visits. Additional PVBs were frequently performed after the first treatment, with over 26 per cent of patients receiving a PVB ten or more times in one year, with almost eight per cent of patients receiving 30 or more. No overall change was found in opioid dosage in the year after PVB was initiated compared to the year before. 

“Frequent use of PVB is common. Initiating treatment with PVCs is associated with marked increases in health care utilization, which includes physician visits and other injection procedures,” explains Dr. Eldon Loh, Lawson Associate Scientist and Physiatrist at St. Joseph’s Health Care London. 

This research provides a broad perspective on the use of PVBs in Ontario, and on the use of nerve blocking treatments in general. There has been a concern for several years about the over use of these procedures; however, this is the first study to systematically document the impact on health care utilization and opioid use. 

"We hope that from this study, the appropriate use of PVBs and other pain interventions will be re-evaluated at a provincial level to ensure the use of health resources is being properly managed and we achieve the best outcome for patients,” Dr. Loh adds. 

The study, “A Retrospective Cohort Study of Healthcare Utilization Associated with Paravertebral Blocks for Chronic Pain Management in Ontario,” is published in the Canadian Journal of Pain. 

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Scientists at Children’s Health Research Institute (a program of Lawson Health Research Institute), Sunnybrook Research Institute and The Hospital for Sick Children (SickKids) are working together to study the potential benefits of inhaled sedation as an alternative to keep critically ill children sedated and comfortable.

“Many sick children need support from a ventilator and other life-saving treatments, and may require intravenous (IV) sedatives to tolerate these uncomfortable therapies,” says Dr. Rishi Ganesan, Lawson Associate Scientist and Paediatric Neurocritical Care Physician at Children’s Hospital at London Health Sciences Centre (LHSC). “However, our current sedation options may contribute to a complication called delirium. We are interested in evaluating if delirium and long-term neurological complications are lower in children receiving inhaled sedation compared to those receiving IV sedation, which is the current standard of care.” 

Delirium is an acute change in mental state that children in critical care can sometimes develop as a result of their critical illness and the medications and therapies they receive during their hospital stay. Delirium presents as confusion, disorientation, agitation, excessive drowsiness or poor attention. Dr. Marat Slessarev, Lawson Scientist and Critical Care Physician at LHSC, has been researching and comparing inhaled sedation to IV sedation in adults since the pandemic hit in 2020 in a collaborative trial called SAVE-ICU with Dr. Angela Jerath, Anesthesiologist and Scientist at Sunnybrook.

“One of the challenges with IV sedation is that we do not have a way to measure the level of sedatives in the blood,” explains Dr. Slessarev. “Critically ill patients that are sedated can sometimes develop issues with the kidney and liver, which are both important in eliminating the sedatives from the blood stream.”

Through this novel collaborative research, the team is now looking at the potential benefits of inhaled sedation in paediatric patients.

“Inhaled sedatives are an alternative to currently used IV sedatives, and they may reduce delirium and accelerate brain recovery. Inhaled sedatives are used safely every day in operating rooms, widely available and inexpensive,” explains Dr. Jerath. “In contrast to IV sedatives, they do not accumulate in the body, are rapidly eliminated via the lungs, promote faster awakening and discharge from a ventilator, and reduce inflammation – which may be a contributing factor to delirium.”

Enrollment for the ABOVE trial is beginning at Children’s Hospital at LHSC and SickKids. The pilot study will enroll 60 critically ill paediatric patients who will be randomized into two groups; one group will receive inhaled sedation while the other will get standard IV sedation. Once the pilot phase of the trial is complete, the team hopes to expand this trial across the country with more paediatric intensive care units (ICUs) joining the larger trial.

“The field of critical care has made significant strides in life-saving technologies and therapies in recent years, but now we are focused on finding ways to ensure our patients continue to do well after leaving the hospital,” says Dr. Nicole McKinnon, Critical Care Physician and lead investigator at SickKids and a Scientist Track Investigator at SickKids Research Insitute. “This trial is a first step in better understanding the effects of sedative and pain medications on children’s longer-term neurocognitive development. Our research will be key to providing critically ill children with the greatest chance to flourish at home.”

“This has the potential to change how critically ill children are cared for in paediatric ICUs across Canada and the world,” adds Dr. Ganesan. “We hope that inhaled sedation makes a difference in children’s long-term functional outcomes, so they can thrive and achieve their full potential.” 

The ABOVE Trial recently received funding through a Canadian Institute for Health Research (CIHR) grant.

About Sunnybrook Research Institute: Sunnybrook Research Institute (SRI) is the research arm of Sunnybrook Health Sciences Centre, an internationally recognized academic health sciences centre fully affiliated with the University of Toronto. With well-established programs in basic and applied sciences which span across three scientific platforms and ten clinical programs, SRI is developing innovations in care for the more than 1.3 million patients the hospital cares for annually. To learn more, visit www.sunnybrook.ca/research

About The Hospital for Sick Children: The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is a founding member of Kids Health Alliance, a network of partners working to create a high quality, consistent and coordinated approach to paediatric health care that is centred around children, youth and their families. SickKids is proud of its vision for Healthier Children. A Better World.

LONDON, ONTARIO - A team from Lawson Health Research Institute and Western University has made significant steps forward in understanding COVID-19 through two back-to-back studies published this week in Critical Care Explorations. In one study, the team has identified six molecules that can be used as biomarkers to predict how severely ill a patient will become. In the other study, they are the first to reveal a new mechanism causing blood clots in COVID-19 patients and potential ways to treat them. 

The studies were conducted by analyzing blood samples from critically ill patients at London Health Sciences Centre (LHSC). They build on a growing body of work from the team who were first in the world to profile the body’s immune response to the virus by revealing a separate six molecules that could act as potential targets to treat hyperinflammation in critically ill patients. 

“We’ve begun answering some of the biggest COVID-19 questions asked by clinicians and health researchers,” says Dr. Douglas Fraser, lead researcher from Lawson and Western’s Schulich School of Medicine & Dentistry, and Critical Care Physician at LHSC. “While the findings need to be validated with larger groups of patients, they could have important implications for treating and studying this disease.”

Predicting which COVID-19 patients will get worse

With no proven therapies, many COVID-19 patients admitted to intensive care units (ICUs) do not survive. 

“When a patient is admitted to ICU, we normally wait to see if they are going to get worse before we consider any risky interventions. To improve outcomes, we not only need new therapies but also a way to predict prognosis or which patients are going to get worse,” explains Dr. Fraser. 

The researchers identified six molecules of importance (CLM-1, IL12RB1, CD83, FAM3B, IGFR1R and OPTC). They found that these molecules were elevated in COVID-19 patients who would become even more severely ill. They found that when measured on a COVID-19 patient’s first day of ICU admission, the molecules could be used to predict which patients will survive following standard ICU treatment.

“While further research is needed, we’re confident in these biomarkers and suspect these patterns may be present even before ICU admission, such as when a patient first presents to the emergency department,” notes Dr. Fraser. “These findings could be incredibly important in determining how severely ill a patient will become.”

The team measured 1,161 plasma proteins from the blood of 30 participants: 10 COVID-19 patients and 10 patients with other infections admitted to LHSC’s ICU, as well as 10 healthy control participants. Blood was drawn on set days of ICU admission, processed in a lab and then analyzed using statistical methods and artificial intelligence. 

The team notes that predicting a patient’s disease severity can help in a number of ways. It could allow for medical teams to have important conversations with family members, setting goals of care based on the patient’s health and personal wishes. Medical teams could use the knowledge to mobilize resources more quickly. If they know a patient is at higher risk of death, they may consider intervening sooner despite associated risks. The team also hopes the findings can be used to better design COVID-19 clinical trials by grouping patients based on their risk. This could allow for stronger results when examining potential treatments for the disease. 

Understanding why blood clots occur and how to treat them

A major complication occurring in most critically ill COVID-19 patients is clotting in the lung’s small blood vessels which leads to low oxygen levels in the body. 

“The reason for this clotting has been unclear. Most suspect the clotting mechanisms in our blood are put into overdrive and so many clinicians have been treating with anticoagulant therapies like the drug heparin,” says Dr. Fraser. “But we’ve uncovered an entirely different mechanism.”

The team further analyzed the blood samples from their 30 participants, and found evidence to suggest that the inner linings of small blood vessels are becoming damaged and inflamed, making them a welcoming environment for platelets (small blood cells) to stick. 

They discovered that COVID-19 patients had elevated levels of three molecules (hyaluronic acid, syndecan-1 and P-selectin.) The first two molecules are products broken down from small hair-like structures (the glycocalyx) which line the inside of the blood vessels. Their presence suggests the glycocalyx is being damaged with its breakdown products sent into the bloodstream. The presence of P-selectin is also significant as this molecule helps to make both platelets and the inner lining of blood vessels adhere to one another. 

“The glycocalyx keeps platelets from touching the inside wall of the blood vessel and helps facilitate the production of nitric oxide, which has an important role in preventing platelets from sticking,” explains Dr. Fraser.  “We suspect the body’s immune response is producing enzymes that shear off these little hair-like structures, inflaming blood vessels and making them a welcoming environment for platelets to form clots.”

The team suggests that two therapies may hold promise for treating blood clots in COVID-19 patients: platelet inhibitors to stop platelets from sticking and molecules to protect and restore the inner lining of blood vessels.

“By exploring these therapies as potential alternatives to anticoagulant therapies, we may be able to improve patient outcomes,” says Dr. Fraser. “Through our combined findings, we hope to provide tools to predict which patients will become the most severely ill and treatments for both hyperinflammation and blood clots.”

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Dr. Douglas Fraser, Researcher from Lawson Health Research Institute and Western University’s Schulich School of Medicine & Dentistry

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