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Early restrictive fluid management does not reduce mortality in sepsis-induced hypotension

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1. Early use of vasopressors combined with a conservative fluid resuscitation did not result in a mortality benefit over a liberal fluid resuscitation strategy. 

2. Early use of vasopressors combined with conservative fluid resuscitation also did not result in significantly different adverse event outcomes compared to liberal fluid resuscitation. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: Sepsis-induced hypotension often requires admission to the intensive care unit due to hemodynamic instability. Extravasation of intravascular volume into the third space often results in drops in blood pressure, as seen in sepsis-induced hypotension. Fluid resuscitation and the use of vasopressors have been pillars in its management, with the primary goal of maintaining adequate intravascular volume to provide effective circulation. For many patients, both strategies are employed. However, it is unclear whether the approach of initiating vasopressors earlier in the course with a conservative strategy of fluid resuscitation will lead to better mortality benefits when compared with the alternative of being liberal with fluid resuscitation prior to initiating vasopressors later in the course. This study compared these two approaches among adults presenting with sepsis-induced hypotension. The primary outcome of interest was whether one approach yielded a greater mortality benefit at 90-days after the initial event. Results of the study found that there was no difference in 90-day mortality outcome or secondary outcomes of interest between the two modalities. This study was limited in that it excluded patients with extreme volume contraction and those who received more than 3L of fluids in the prehospital setting. Therefore, the results of the study have limited generalizability.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This study was a multicenter, randomized controlled trial comparing the mortality benefit of two different approaches to managing sepsis-induced hypotension: i) early vasopressor use and conservative fluid management, and ii) liberal fluid resuscitation prior to initiating vasopressor use. All adults with septic-induced hypotension were eligible for the study. Participants with confounding features to the study question were excluded. Those who were screened more than four hours after meeting the criteria for refractory hypotension or more than 24 hours since the first presentation, those who received more than 3L of IV fluids, those who were volume overloaded, and those who were significantly volume contracted from non-sepsis causes. After applying the inclusion and exclusion criteria, 1,563 participants were assigned randomly in a 1:1 ratio to one of the two strategies. The primary outcome was all-cause mortality before discharge at 90 days after the inciting event. Secondary outcomes of interest focused on adverse effects, which included duration of time without ventilator use, renal-replacement therapy, vasopressor use, and discharge from the intensive care unit. Results of the study found that at 90 days, there was no significant difference in all-cause mortality between the two groups (estimated difference, -0.9%; 95% Confidence Interval [CI], -4.4 to 2.6; p=0.61). The secondary analysis found similar results of non-superiority between one strategy over another. In summary, this study suggests that there is no difference between the two approaches to sepsis-induced hypotension.

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©2023 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

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Canada to donate up to 200,000 vaccine doses to combat mpox outbreaks in Africa

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The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.

It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.

Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”

Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.

Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.

A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.

On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.

Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”

But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”

“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.

Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.

Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.

Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.

“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.

“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”

This report by The Canadian Press was first published Sept. 13, 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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How many Nova Scotians are on the doctor wait-list? Number hit 160,000 in June

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HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.

The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.

Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.

“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”

The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.

A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.

Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.

“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.

Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.

The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.

“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.

This report by The Canadian Press was first published Sept. 11, 2024.

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Newfoundland and Labrador monitoring rise in whooping cough cases: medical officer

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ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.

Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.

Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.

Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.

The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.

“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.

Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.

Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.

Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.

A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.

This report by The Canadian Press was first published Sept. 10, 2024.

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