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Adrenaline can save a heart but hurts the brain. Canadian research aims to find best dose for a potent drug

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When Dan Shire’s heart stopped beating in 2016, it led to a race against time to save his life.

Shire’s wife heard him struggling to breathe in the middle of the night. Then she ran to the phone to call 911, started CPR, and waited minute-by-painful-minute for first responders to show up.

Once paramedics arrived at the couple’s Pickering, Ont., home, they used a defibrillator on Shire four times, then tried a potent medication in an attempt to restart his heart.

That drug, epinephrine — also called adrenaline — is given intravenously every three to five minutes, up to an average of six milligrams. It stimulates blood flow by squeezing the blood vessels, which can, in some cases, help get someone’s heart beating again.

But researchers worry there’s a dangerous ripple effect: When you save someone’s heart, you can hurt their brain. Studies suggest higher doses of epinephrine might actually cause neurological damage.

In Shire’s case, he survived his episode of cardiac arrest and now leads a largely normal life. But the 67-year-old does have cognitive impacts such as short-term memory issues and some difficulty with complex tasks like driving. He’s not sure how much of that is from his heart stopping — cutting off oxygen to his brain for the better part of 16 minutes — or the dose of epinephrine he was given.

When Dan Shire’s heart stopped beating in 2016, it led to a race against time to save his life. Paramedics gave him epinephrine. He survived, but with some cognitive impacts. (Turgut Yeter/CBC)

To give cardiac arrest patients the best chance at not only survival, but also a high quality of life, Canadian researchers have launched a massive, years-long trial to find the “sweet spot” for epinephrine usage.

“There could be a tendency that [first responders] are erring on the side of giving you as aggressive a treatment as possible to save your life in that moment,” said Shire.

“A month later, you might find yourself in the position where you had too much epinephrine, and now have problems with cognitive outcomes.”

Trial will include multiple provinces

Dubbed EpiDose, the randomized controlled trial involves paramedic teams in B.C., Ontario, and eventually more provinces. Each time those teams encounter a patient with cardiac arrest, they’ll randomly provide either a higher or lower dose of epinephrine.

Then researchers will track the results, not just to see which lives are saved, but to find out about their brain function afterwards.

It’s the latest in a set of ongoing studies on epinephrine from a research team co-led by Dr. Steve Lin, the interim chief of emergency medicine at St. Michael’s Hospital, a part of Unity Health Toronto.

The team is hoping to include data on nearly 4,000 randomly-selected patients — a process that could take five to six years.

 

Study aims to find best adrenaline dose for cardiac arrest patients

 

The drug epinephrine — or adrenaline — can increase a person’s chances of survival and full recovery after a cardiac arrest, but the optimal dose isn’t really known. A new study is equipping some paramedics in Ontario and B.C. with different doses of the drug to help determine the answer.

Lin said the researchers are proposing a new “ceiling” for the standard dose, if the results suggest that a lower dose of two milligrams in total works just as well or better than the current standard of six milligrams. His team will then be contacting survivors to see how their bout of cardiac arrest impacted their life, including their later neurological function.

That’s another reason why the trial will take years: Survivors will be few and far between. When it comes to cardiac arrest, most people don’t make it, with only an estimated 10 per cent of patients surviving if their heart stops outside of a hospital.

“Cardiac arrest is the most deadly condition, right?” noted Lin. “It’s when your heart actually stops beating. And if left untreated, patients will certainly die.”

Optimizing the dose

Epinephrine can save lives, he stressed, particularly when it’s used following first-response measures like cardiopulmonary resuscitation (CPR) and a defibrillator, which applies an electric charge to help a stopped heart start beating. But Lin is hopeful that a smaller epinephrine dose might optimize outcomes, allowing the medication to help restart the heart without damaging later brain function.

One randomized trial looking at epinephrine use for out-of-hospital cardiac arrest, published in 2018 in the New England Journal of Medicine, found the overall rate of survival 30 days later was slightly better in the group given epinephrine — up to an average of close to five milligrams — compared to those given a placebo.

But there were also noticeable differences in the groups’ brain function. Close to a third of those given epinephrine ended up with severe neurological disability, compared to less than 18 per cent in the placebo group.

“There is some evidence that there might be very high doses given that can harm the brain, because you squeeze the blood vessel so much that it starts to decrease blood flow to the brain itself,” Lin said.

“I think we can actually do better.”

How to do basic CPR when someone’s heart stops

 

When someone goes into cardiac arrest, cardiopulmonary resuscitation, or CPR, is one of the best ways to give them a shot at survival. Chris Schmied from St. John’s Ambulance walks health reporter Lauren Pelley through the basic steps.

‘These are really tough calls’

Sitting in the back of an ambulance in Oakville, Ont., longtime Halton Region paramedic Olena Campeau holds up one of the study kits: A white box labeled EpiDose, with no further information on what’s inside. It’s only when paramedics open the kit that they’ll learn which treatment arm a patient is assigned to, Campeau explained.

Halton Region was among the first paramedic teams to sign onto the trial, alongside services in Peel, Toronto, Ottawa and British Columbia Emergency Health Services.

Longtime Halton Region paramedic Olena Campeau is part of one of the first responder teams who are participating in the EpiDose study. Conducting this kind of research is crucial, she says, but it comes with challenges. (Turgut Yeter/CBC)

Conducting this kind of research is crucial, but it comes with challenges, she added. Cardiac arrest calls are fast-paced — since every moment counts when it comes to survival rates — and can happen anywhere.

“I attended to a cardiac arrest on a patient at an outdoor climbing wall,” Campeau said. “These are really tough calls for paramedics.”

The patients themselves are also unconscious, which adds another layer of complexity to the EpiDose research since people can’t actually give verbal or written consent to participate.

There’s also no time for paramedics to get a sign-off from someone’s family members, Lin noted, and that’s assuming anyone who knows the patient is even present.

Typically, advance consent from participants is a hallmark of medical studies like this. But since cardiac arrest is so deadly — and concrete research on the ideal epinephrine dose is so lacking — Lin said the team’s research is allowed under strict research ethics guidelines.

Surviving patients, or a deceased patient’s family, will be alerted after the fact, and patient information collected during the trial will also be de-identified and replaced by a unique study number to keep patients’ identities private.

The study was approved by the Sunnybrook Research Ethics Board, which means it meets federal guidelines for ethical research involving humans.

Kits for the EpiDose trial contain either a larger or smaller dose of epinephrine, but paramedics don’t know until they open the kit which dose the patient will get. That way, the patients are randomly assigned to get more or less of the potent drug. (Lauren Pelley/CBC)

Study could ‘change treatment’ approach globally

Emergency physician Dr. Benjamin Abella, director of the Center for Resuscitation Science at the University of Pennsylvania, said while adrenaline has been a cornerstone of cardiac arrest treatment for many years, it’s never been put to a proper clinical trial.

Animal models, and more recent human data, do suggest the drug improves initial survival rates, he noted — as in simply bringing back someone’s pulse. “But it leads to way more neurological injuries. That has to be really considered in how we approach patients with cardiac arrest.”

If someone near you goes into cardiac arrest, your quick actions could help save their life. Dr. Roopinder Sandhu, professor in cardiac sciences at the University of Calgary, shares what you need to know about basic life support and how to prevent cardiac arrest.  For transcripts of The Dose, please visit: lnk.to/dose-transcripts. Transcripts of each episode will be made available by the next workday.

Abella, who isn’t involved in the EpiDose trial, welcomed deeper research into how well epinephrine works, given that hundreds of thousands of people across North America experience cardiac arrest in any given year.

“Dosing and timing of epinephrine are both really open questions, and we don’t have the answers,” he said. “I’m old enough to remember a time when dosing for epinephrine was much higher during cardiac arrest in the guidelines than what we do currently. And so that was changed — and it may need to change yet again.”

Lin and Campeau are both optimistic that the EpiDose trial could eventually reshape how paramedics tackle situations where someone’s heart has stopped beating, and even inform global clinical guidelines for how to best use epinephrine.

“We know that this is a crucial study,” Campeau said. “It can change treatment for cardiac patients across Canada, and possibly worldwide.”

 

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Health Canada approves updated Moderna COVID-19 vaccine

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TORONTO – Health Canada has authorized Moderna’s updated COVID-19 vaccine that protects against currently circulating variants of the virus.

The mRNA vaccine, called Spikevax, has been reformulated to target the KP.2 subvariant of Omicron.

It will replace the previous version of the vaccine that was released a year ago, which targeted the XBB.1.5 subvariant of Omicron.

Health Canada recently asked provinces and territories to get rid of their older COVID-19 vaccines to ensure the most current vaccine will be used during this fall’s respiratory virus season.

Health Canada is also reviewing two other updated COVID-19 vaccines but has not yet authorized them.

They are Pfizer’s Comirnaty, which is also an mRNA vaccine, as well as Novavax’s protein-based vaccine.

This report by The Canadian Press was first published Sept. 17, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

The Canadian Press. All rights reserved.

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These people say they got listeria after drinking recalled plant-based milks

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TORONTO – Sanniah Jabeen holds a sonogram of the unborn baby she lost after contracting listeria last December. Beneath, it says “love at first sight.”

Jabeen says she believes she and her baby were poisoned by a listeria outbreak linked to some plant-based milks and wants answers. An investigation continues into the recall declared July 8 of several Silk and Great Value plant-based beverages.

“I don’t even have the words. I’m still processing that,” Jabeen says of her loss. She was 18 weeks pregnant when she went into preterm labour.

The first infection linked to the recall was traced back to August 2023. One year later on Aug. 12, 2024, the Public Health Agency of Canada said three people had died and 20 were infected.

The number of cases is likely much higher, says Lawrence Goodridge, Canada Research Chair in foodborne pathogen dynamics at the University of Guelph: “For every person known, generally speaking, there’s typically 20 to 25 or maybe 30 people that are unknown.”

The case count has remained unchanged over the last month, but the Public Health Agency of Canada says it won’t declare the outbreak over until early October because of listeria’s 70-day incubation period and the reporting delays that accompany it.

Danone Canada’s head of communications said in an email Wednesday that the company is still investigating the “root cause” of the outbreak, which has been linked to a production line at a Pickering, Ont., packaging facility.

Pregnant people, adults over 60, and those with weakened immune systems are most at risk of becoming sick with severe listeriosis. If the infection spreads to an unborn baby, Health Canada says it can cause miscarriage, stillbirth, premature birth or life-threatening illness in a newborn.

The Canadian Press spoke to 10 people, from the parents of a toddler to an 89-year-old senior, who say they became sick with listeria after drinking from cartons of plant-based milk stamped with the recalled product code. Here’s a look at some of their experiences.

Sanniah Jabeen, 32, Toronto

Jabeen says she regularly drank Silk oat and almond milk in smoothies while pregnant, and began vomiting seven times a day and shivering at night in December 2023. She had “the worst headache of (her) life” when she went to the emergency room on Dec. 15.

“I just wasn’t functioning like a normal human being,” Jabeen says.

Told she was dehydrated, Jabeen was given fluids and a blood test and sent home. Four days later, she returned to hospital.

“They told me that since you’re 18 weeks, there’s nothing you can do to save your baby,” says Jabeen, who moved to Toronto from Pakistan five years ago.

Jabeen later learned she had listeriosis and an autopsy revealed her baby was infected, too.

“It broke my heart to read that report because I was just imagining my baby drinking poisoned amniotic fluid inside of me. The womb is a place where your baby is supposed to be the safest,” Jabeen said.

Jabeen’s case is likely not included in PHAC’s count. Jabeen says she was called by Health Canada and asked what dairy and fresh produce she ate – foods more commonly associated with listeria – but not asked about plant-based beverages.

She’s pregnant again, and is due in several months. At first, she was scared to eat, not knowing what caused the infection during her last pregnancy.

“Ever since I learned about the almond, oat milk situation, I’ve been feeling a bit better knowing that it wasn’t something that I did. It was something else that caused it. It wasn’t my fault,” Jabeen said.

She’s since joined a proposed class action lawsuit launched by LPC Avocates against the manufacturers and sellers of Silk and Great Value plant-based beverages. The lawsuit has not yet been certified by a judge.

Natalie Grant and her seven year-old daughter, Bowmanville, Ont.

Natalie Grant says she was in a hospital waiting room when she saw a television news report about the recall. She wondered if the dark chocolate almond milk her daughter drank daily was contaminated.

She had brought the girl to hospital because she was vomiting every half hour, constantly on the toilet with diarrhea, and had severe pain in her abdomen.

“I’m definitely thinking that this is a pretty solid chance that she’s got listeria at this point because I knew she had all the symptoms,” Grant says of seeing the news report.

Once her daughter could hold fluids, they went home and Grant cross-checked the recalled product code – 7825 – with the one on her carton. They matched.

“I called the emerg and I said I’m pretty confident she’s been exposed,” Grant said. She was told to return to the hospital if her daughter’s symptoms worsened. An hour and a half later, her fever spiked, the vomiting returned, her face flushed and her energy plummeted.

Grant says they were sent to a hospital in Ajax, Ont. and stayed two weeks while her daughter received antibiotics four times a day until she was discharged July 23.

“Knowing that my little one was just so affected and how it affected us as a family alone, there’s a bitterness left behind,” Grant said. She’s also joined the proposed class action.

Thelma Feldman, 89, Toronto

Thelma Feldman says she regularly taught yoga to friends in her condo building before getting sickened by listeria on July 2. Now, she has a walker and her body aches. She has headaches and digestive problems.

“I’m kind of depressed,” she says.

“It’s caused me a lot of physical and emotional pain.”

Much of the early days of her illness are a blur. She knows she boarded an ambulance with profuse diarrhea on July 2 and spent five days at North York General Hospital. Afterwards, she remembers Health Canada officials entering her apartment and removing Silk almond milk from her fridge, and volunteers from a community organization giving her sponge baths.

“At my age, 89, I’m not a kid anymore and healing takes longer,” Feldman says.

“I don’t even feel like being with people. I just sit at home.”

Jasmine Jiles and three-year-old Max, Kahnawake Mohawk Territory, Que.

Jasmine Jiles says her three-year-old son Max came down with flu-like symptoms and cradled his ears in what she interpreted as a sign of pain, like the one pounding in her own head, around early July.

When Jiles heard about the recall soon after, she called Danone Canada, the plant-based milk manufacturer, to find out if their Silk coconut milk was in the contaminated batch. It was, she says.

“My son is very small, he’s very young, so I asked what we do in terms of overall monitoring and she said someone from the company would get in touch within 24 to 48 hours,” Jiles says from a First Nations reserve near Montreal.

“I never got a call back. I never got an email”

At home, her son’s fever broke after three days, but gas pains stuck with him, she says. It took a couple weeks for him to get back to normal.

“In hindsight, I should have taken him (to the hospital) but we just tried to see if we could nurse him at home because wait times are pretty extreme,” Jiles says, “and I don’t have child care at the moment.”

Joseph Desmond, 50, Sydney, N.S.

Joseph Desmond says he suffered a seizure and fell off his sofa on July 9. He went to the emergency room, where they ran an electroencephalogram (EEG) test, and then returned home. Within hours, he had a second seizure and went back to hospital.

His third seizure happened the next morning while walking to the nurse’s station.

In severe cases of listeriosis, bacteria can spread to the central nervous system and cause seizures, according to Health Canada.

“The last two months have really been a nightmare,” says Desmond, who has joined the proposed lawsuit.

When he returned home from the hospital, his daughter took a carton of Silk dark chocolate almond milk out of the fridge and asked if he had heard about the recall. By that point, Desmond says he was on his second two-litre carton after finishing the first in June.

“It was pretty scary. Terrifying. I honestly thought I was going to die.”

Cheryl McCombe, 63, Haliburton, Ont.

The morning after suffering a second episode of vomiting, feverish sweats and diarrhea in the middle of the night in early July, Cheryl McCombe scrolled through the news on her phone and came across the recall.

A few years earlier, McCombe says she started drinking plant-based milks because it seemed like a healthier choice to splash in her morning coffee. On June 30, she bought two cartons of Silk cashew almond milk.

“It was on the (recall) list. I thought, ‘Oh my God, I got listeria,’” McCombe says. She called her doctor’s office and visited an urgent care clinic hoping to get tested and confirm her suspicion, but she says, “I was basically shut down at the door.”

Public Health Ontario does not recommend listeria testing for infected individuals with mild symptoms unless they are at risk of developing severe illness, such as people who are immunocompromised, elderly, pregnant or newborn.

“No wonder they couldn’t connect the dots,” she adds, referencing that it took close to a year for public health officials to find the source of the outbreak.

“I am a woman in my 60s and sometimes these signs are of, you know, when you’re vomiting and things like that, it can be a sign in women of a bigger issue,” McCombe says. She was seeking confirmation that wasn’t the case.

Disappointed, with her stomach still feeling off, she says she decided to boost her gut health with probiotics. After a couple weeks she started to feel like herself.

But since then, McCombe says, “I’m back on Kawartha Dairy cream in my coffee.”

This report by The Canadian Press was first published Sept. 16, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

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B.C. mayors seek ‘immediate action’ from federal government on mental health crisis

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VANCOUVER – Mayors and other leaders from several British Columbia communities say the provincial and federal governments need to take “immediate action” to tackle mental health and public safety issues that have reached crisis levels.

Vancouver Mayor Ken Sim says it’s become “abundantly clear” that mental health and addiction issues and public safety have caused crises that are “gripping” Vancouver, and he and other politicians, First Nations leaders and law enforcement officials are pleading for federal and provincial help.

In a letter to Prime Minister Justin Trudeau and Premier David Eby, mayors say there are “three critical fronts” that require action including “mandatory care” for people with severe mental health and addiction issues.

The letter says senior governments also need to bring in “meaningful bail reform” for repeat offenders, and the federal government must improve policing at Metro Vancouver ports to stop illicit drugs from coming in and stolen vehicles from being exported.

Sim says the “current system” has failed British Columbians, and the number of people dealing with severe mental health and addiction issues due to lack of proper care has “reached a critical point.”

Vancouver Police Chief Adam Palmer says repeat violent offenders are too often released on bail due to a “revolving door of justice,” and a new approach is needed to deal with mentally ill people who “pose a serious and immediate danger to themselves and others.”

This report by The Canadian Press was first published Sept. 16, 2024

The Canadian Press. All rights reserved.

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