Tag: sepsis

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Promising Advances in Accurately Diagnosing Sepsis

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Doctors in the UK have identified promising evidence for the effectiveness of an early and rapid diagnostic test for sepsis.

Sepsis is a serious complication arising from infection, which can swiftly progress to life-threatening organ failure and is responsible for around 48 000 deaths annually in England. Recent findings, published today in The Lancet Respiratory Medicine, demonstrate that an accessible clinical decision-making tool significantly reduced mortality, with the greatest benefit seen among patients from the most deprived communities. However, the study also showed no difference in the speed of intravenous antibiotic initiation, despite initial expectations.

Diagnosing sepsis in emergency departments remains difficult, as many non-infectious illnesses can mimic its symptoms and there is currently no definitive diagnostic test. This uncertainty contributes to both over- and underdiagnosis. In both situations, delayed treatment can cost lives, while rapid antibiotics are required for those with confirmed sepsis some patients may be treated for sepsis unnecessarily, contributing to the urgent global issue of antimicrobial resistance (AMR). At the same time, misdiagnosis can lead to a failure to correctly identify and treat the actual underlying condition.

A procalcitonin‑guided algorithm is a clinical decision‑making tool that uses levels of the biomarker procalcitonin (PCT) to help guide antibiotic therapy in patients with suspected bacterial infections. However, it is not currently recommended for use in emergency settings because previous research has been inconsistent.

To address this gap, the research team conducted a large, controlled trial which randomised 7667 patients who presented to emergency departments with suspected sepsis. The study tested whether adding the rapid procalcitonin-guided algorithm testing to current clinical practice could help clinicians recognise sepsis more accurately, reduce unnecessary antibiotic prescribing, and maintain at least the same level of patient safety, measured by overall mortality.

The study shows:

  • There was a 17% relative reduction in mortality from 16.6% to 13.6% which means for every 1000 patient treated as suspected sepsis, 31 lives are potentially saved.
  • Patients from the most deprived areas experienced the greatest mortality benefit. Existing research explores inequality in sepsis outcomes, and this latest research may help to overcome identified systemic biases.
  • Importantly, the trial found that regardless of whether patients were treated with the procalcitonin‑guided algorithm or received standard care, there was no difference in how quickly intravenous antibiotics were started. Although the research team had anticipated that the algorithm might improve early antibiotic initiation, the trial showed it did not – a key finding, given this was one of the co‑primary outcomes.

Co-chief investigator, Dr Stacy Todd, Consultant in Infectious Diseases and General Medicine, NHS University Hospitals of Liverpool Group, said: “The evidence supports the value of early and rapid diagnostics and indicates a need for further biomarker and algorithm development. Uptake of procalcitonin-guided care into health systems will now depend on greater understanding of the mechanism of effect, further health economic evaluations, and robust implementation frameworks.”

Source: University of Liverpool

Categories : Emergency MedicineTags :

Potential New Treatment for Sepsis Shows Promise in Trial

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Griffith University researchers may have unlocked the secret to treating sepsis, with a Phase II clinical trial in China successfully concluding with promising results.

Photo by Alex Fedini on Pixabay

Griffith University researchers may have unlocked the secret to treating sepsis, with a Phase II clinical trial in China successfully concluding with promising results. The sepsis drug candidate, a carbohydrate-based drug called STC3141, was co-developed by Distinguished Professor Mark von Itzstein AO and his team from Griffith’s Institute for Biomedicine and Glycomics, and Professor Christopher Parish and his team at The Australian National University.

“The trial met the key endpoints to indicate the drug candidate was successful in reducing sepsis in humans,” Professor von Itzstein said.

STC3141 was administered as an infusion via a cannula and counteracted a significant biological molecule release phenomenon which occurred in the body during the course of sepsis.

The small-molecule experimental drug was a carbohydrate-based molecule and could treat sepsis by reversing organ damage.

Sepsis was known to affect millions of hospitalised patients across the world each year and occurred when the body’s immune response to an infection attacked and injured its own tissues and organs.

“When sepsis is not recognised early and managed promptly, it can lead to septic shock, multiple organ failure and death,” Distinguished Professor von Itzstein said.

The trial, conducted by Grand Pharmaceutical Group Limited (Grand Pharma), involved 180 patients with sepsis, one of the leading causes of death and long-term disability worldwide.

Currently, there is no specific anti-sepsis therapy available, and sepsis is considered a clinical unmet need.

Professor von Itzstein said Grand Pharma would now look to progress to a Phase III trial to continue testing the efficacy of the novel treatment.

“It’s hoped we could see the treatment reach the market in a handful years, potentially saving millions of lives,” he said.

Executive Director of the Institute for Biomedicine and Glycomics, Professor Paul Clarke, said: “I am thrilled to see the results of the trial which ultimately aims to save lives.”

“The Institute and its researchers collectively work on translational research to deliver real and immediate impacts both in Australia, and globally to transform lives.”

Source: Griffith University

Categories : Immune SystemTags :

Immunometabolism Might Hold the Key to Controlling Sepsis

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Metabolic changes that “rewire” part of the immune system can intensify sepsis, the body’s dysregulated response to infection. This discovery may lead to new ways to block metabolic changes contributing to excessive and ineffective inflammation, reset the immune system, and bring sepsis under control, researchers at Vanderbilt Health reported January 15 in the journal Nature Immunology.

“Metabolism is potentially a means by which we could intervene in immune dysfunction in ICU (intensive care unit) patients including those with sepsis,” said the paper’s first and co-corresponding author, Matthew Stier, MD, PhD, assistant professor of Medicine in the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt Health.

“I think we can make great progress and great strides by aligning cutting-edge basic science tools with ICU patient samples to understand these mechanisms and prioritise therapies for future interventions,” he said.

Sepsis is characterised by the massive production and release of inflammatory molecules, including cytokines, that if unchecked, can lead to tissue damage, septic shock, organ failure, and death.

Despite decades of research focused on stopping this “cytokine storm” and hyperinflammation, “we have unfortunately not been able to identify successful drug therapies in sepsis,” said Stier, a physician-scientist who focuses on immunologic and metabolic dysfunction in critical illness. Targeting the inflammatory aspect of sepsis is likely important, but by itself may not be sufficient.

“We provide antibiotics and great supportive care to weather the cytokine storm,” he said, “but that doesn’t fully resolve the problem. It keeps people alive while we wait for their bodies to fix themselves — or not.”

In critical illness, including sepsis, the body’s normal metabolic processes become impaired. This includes immunometabolism, the energy-generating processes that fuel the immune system.

At the same time, the immune system’s protective functions become exhausted, resulting in an acquired immunosuppression, which leaves patients vulnerable to secondary infections, persistent organ dysfunction, repeated hospitalisations and death.

While prior research has defined the characteristics of metabolism and immune dysfunction, this study was among the first to explore the mechanisms of immunometabolic dysfunction in sepsis and their association with immunosuppression, often called “immunoparalysis.”

Stier and his colleagues used cutting-edge technologies, including single-cell sequencing and flow cytometry, to study immune cells collected from the blood of critically ill patients.

The blood samples were collected and stored through the Sepsis Clinical Resource and Biorepository (SCARAB), a unique, highly collaborative ICU biobank developed by Julie Bastarache, MD, and Lorraine Ware, MD, professors of Medicine in the Division of Allergy, Pulmonary and Critical Care Medicine.

Two of the most important elements of the body’s immune responses are CD4+ T “helper” cells, inflammatory “foot soldiers” of the immune system that are distinguished by the CD4 surface protein they express, and regulatory T (Treg or “suppressor”) cells, which guard against over-active immune responses.

To study the impact of critical illness and sepsis on these cells, the Vanderbilt Health team used SCENITH, a flow cytometry-based method developed by French researchers that enables researchers to functionally profile energy metabolism with single-cell resolution.

“This technique allowed us to do something prior studies hadn’t done … to look at the metabolism of every single cell set on its own and identify subset-specific metabolic adaptations,” Stier said.

The key finding: Treg cells undergo metabolic “reprogramming” in patients with critical illness and sepsis, leading to altered tryptophan metabolism and response to reactive oxygen species in a way that enhances their immunosuppressive capability, at the expense of CD4+ T “helper” cells.

“The metabolic turmoil of critical illness appears to give Treg cells a survival and functional advantage, contributing to the harmful immunoparalysis seen in sepsis,” he said.

“This is very much a preclinical paper,” Stier cautioned. Yet it demonstrates the feasibility of deeply dissecting immunometabolic mechanisms using ICU patient biospecimens and highlights the importance of such insights to prioritise future therapeutic targets in critical illness and sepsis, he said.

Source: Vanderbilt University Medical Center

Categories : HIVTags :

Trial Suggests Simple Treatment Change for HIV-related Sepsis

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Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash

A University of Virginia-led team of researchers has made a discovery that may change sepsis treatment for patients in Africa.

Over the course of five years, the researchers studied patients with HIV-related sepsis in eastern Africa, discovering that the most common cause of sepsis was tuberculosis and that treating it immediately, even before a tuberculosis diagnosis was made, significantly improved survival rates. 

Sepsis, or critical illness due to infection, is the leading global cause of death, responsible for an estimated one-fifth of deaths worldwide.

“We designed a trial with colleagues in Tanzania and Uganda to look specifically at people living with HIV, who suffer higher rates of sepsis and are more likely to die when they contract it,” said Dr Scott Heysell, director of the UVA Center for Global Health Equity and the co-lead investigator of the study. “Over half of the people enrolled in this trial were ultimately found to have tuberculosis and, if they immediately received tuberculosis treatment, they were significantly more likely to survive.”

Funded by a grant from the National Institutes of Health, the research, dubbed the “ATLAS study,” was done by a team of nearly 30 doctors, nurses, pharmacists, study coordinators and statisticians, including leading HIV and tuberculosis physician-scientists, Dr Stellah Mpagama from Kibong’oto Infectious Diseases Hospital in Tanzania, and Dr Conrad Muzoora, from the Mbarara University of Science and Technology in Uganda.

“The trial is the culmination of almost 20 years of collaborative work with colleagues in Uganda and Tanzania to better understand, diagnose and manage sepsis,” said co-lead investigator Dr Christopher Moore, professor of medicine and global health equity at the UVA School of Medicine. “The results of ATLAS have broad and significant implications for the treatment of sepsis in Africa, an all too common and deadly illness, which sadly is likely to become even more common with the advent of global public health funding cuts.”

It is often difficult to diagnose tuberculosis, so the team had to use newer and more exhaustive testing, according to Heysell.

“It is a tragedy to be on the front lines and witness the excessive mortality and morbidity from sepsis and tuberculosis, particularly among people with HIV,” said Dr Tania Thomas, a contributing researcher and associate professor of infectious diseases and international health at UVA. “These are treatable conditions, but time is rarely on our side. Until we have more accurate rapid diagnostic tests for tuberculosis, we are pleased to demonstrate that the strategy of immediate tuberculosis treatment can improve survival.”

The team has received additional NIH funding this year to continue its work through a new trial at four hospitals in Tanzania and Uganda to test whether the use of hydrocortisone to reduce inflammation and improve blood pressure, and/or an immediate treatment for tuberculosis and other bacterial pathogens, will improve 28-day mortality from HIV-related sepsis.

“In programmatic settings, tuberculosis treatment was mostly the same as for people without HIV, even though their health needs are more complex,” said Dr Mpagama. “Many of these patients have multiple infections at the same time, which makes their care more challenging.”

The research is part of UVA’s Center for Global Health Equity’s effort to establish meaningful, two-sided research partnerships in Eastern Africa, according to Heysell, who is working to increase educational and research opportunities outside of the US for UVA students. This includes coordinating clinical electives for medical students and other health science students in hospitals and clinics abroad.

To that end, emergency medicine professor Dr Amita Sudhir has been promoted to inaugural director for global health training within the center. Her goal will be to increase abroad opportunities for medical students within existing partnering organisations.

Source: University of Virginia

Categories : Immune SystemTags :

Researchers Identify New Method to Protect Against Sepsis

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Sepsis is the No.1 cause of death in the intensive care unit of hospitals worldwide and a major concern for health scientists and medical professionals alike.

Dr Scott Widenmaier (PhD), an associate professor in the Department of Anatomy, Physiology and Pharmacology in USask’s College of Medicine, has zeroed in on a specific protein that might be key to helping the body fight back against the potentially life-threatening condition.

By manipulating this protein, researchers believe there is a new avenue to protect patients against sepsis. Widenmaier and his team have had their research recently published in Cellular and Molecular Gastroenterology and Hepatology.

“Sepsis is the largest cause of death in the intensive care unit globally,” Widenmaier said. “Sepsis can cause damage to organs like the heart, kidney, and lungs. It can also cause liver dysfunction, and when this occurs, the liver is not able to properly perform its functions that are useful in helping the body deal with an infection.”

Sepsis is caused by the body’s immune system response to infection causing damage to the body itself. As Widenmaier puts it, many people believe that bacteria or a virus they acquire are what causes people to get sick. However, it’s the body’s response to the infection that results in severe sickness and can escalate to sepsis – what Widenmaier identified as “a dysregulated immune response that leads to life-threatening complications.”

“The immune system releases cytokines and various factors that are trying to kill the bacteria or the virus, but the process of doing it actually dramatically changes our physiology and leads to us being really sick,” Widenmaier said.

While conventional methods for treating sepsis have been targeted at mitigating the infections that might lead to sepsis, Widenmaier said more recent studies have recognised that the body itself has built-in disease tolerance mechanism that could be harnessed to protect itself from the potential damage. In other words, when disease tolerance is working well, the process of killing the infection won’t cause the person to get nearly as sick and preserve healthy organ function.

Widenmaier and his team identified a “transcription factor” protein in the liver called NRF1, which acts as a “molecular switch” to help control the body’s own disease tolerance response. In experimental models infected with E. coli, over-expressing the NRF1 protein led to better overall responses to infection and protection against sepsis.

When over-expressed, the protein enables the liver to secrete more very low-density lipoprotein (VLDL) particles, which better protects organs against damage caused by sepsis. It’s this connection between the NRF1 “switch” and the liver’s production of VLDL that Widenmaier says may be a promising approach to improve the outcomes of patients with sepsis.

“Our lab is very interested in finding ways to either pharmacologically or genetically manipulate NRF1 to promote health,” he said.

Widenmaier credited his team – including colleagues, students and trainees – for their work in identifying this potential target for sepsis treatments and for the resulting research paper.

The next step for this research would be to see how feasible this pathway might be for treatment and whether it is still active in conditions when sepsis is very common – and while they aren’t at the stage of human trials yet, Widenmaier said he wants to delve deeply into this new area in the search for better sepsis care.

“We want to explore this quite intensively,” he said. “There’s a lot of clinical investigators across the country … I’m interested in continuing those connections and trying to strengthen them, and hopefully we can find a place where clinicians and our lab can benefit from the science.”

Source: University of Saskatchewan

Categories : Medical Research & TechnologyTags :

Breakthrough in Sepsis Research: Vitamin B1 Stops Production of Lactate

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Scientists in Ghent, Belgium have made a major breakthrough in sepsis research. In a study on mice, the researchers demonstrate that vitamin B1 (thiamine pyrophosphate, TPP) restores mitochondrial energy metabolism, drastically reduces lactate production, and increases survival rates in sepsis. The study results were published in Cell Reports.

Sepsis, the body’s runaway reaction to an infection, affects vital organs such as the heart, lungs, liver, and kidneys, while patients experience an excessive buildup of lactic acid in the blood.

Each year, sepsis affects 49.5 million people worldwide and claims 11 million lives. To date, there is still no targeted treatment for this condition. New research from the VIB-UGent Center for Inflammation Research may now represent a breakthrough. In a study led by Professor Claude Libert, a Ghent-based research team has discovered a simple yet powerful therapeutic approach: a combination of vitamin B1 and glucose.

Vitamin deficiency causes an energetic blackout 

In 2021, the same research group had already shown that lactic acid accumulates in the blood of sepsis patients because the body can no longer efficiently clear it. Lactic acid is a metabolite that builds up in our muscles after intense physical exercise. Under normal circumstances, lactic acid is processed by the liver, but in sepsis patients, this process comes to a halt. When too much lactic acid remains in the bloodstream, the patient’s blood pressure plummets rapidly, often with fatal consequences.

With a new study, the research group has now uncovered why lactic acid is produced in such large quantities in the first place and how this can be counteracted. The answer turns out to be remarkably simple and clinically relevant: an acute shortage of vitamin B1 in the mitochondria – the cell’s energy factories – forces another molecule, pyruvate, to be converted into lactic acid.

“For the first time, we’ve been able to show that the problem in sepsis is not so much a lack of oxygen, but a fundamental biochemical defect caused by vitamin B1 deficiency,” explains Louise Nuyttens, lead author of the study. “This shuts down the entire energy network in the body and creates a vicious cycle of lactic acid production and organ damage.”

An effective treatment for sepsis 

As the next step, the researchers investigated whether they could restore energy metabolism by administering vitamin B1. In mouse models, they observed that such treatment drastically reduced lactic acid production and improved survival rates. But the real breakthrough came when they combined vitamin B1 with glucose.

“Although it seems logical to give severely ill patients extra glucose, this often leads to more lactic acid production, which is undesirable in sepsis patients. Thanks to vitamin B1, however, we were able to reprogram glucose metabolism. Glucose was safely converted into pyruvate and then into energy, rather than into toxic lactic acid,” explains Louise Nuyttens.

“The results are truly spectacular,” says Prof. Claude Libert. “In our severe sepsis animal models, nearly all mice survived with the combination of vitamin B1 and glucose. This is one of the most powerful metabolic interventions we’ve ever seen, acting on very simple mechanisms that make it quickly translatable to intensive care.”

Bad blood 

Beyond its scientific impact, the societal relevance is also significant. These new insights may offer a path toward a globally applicable therapy for a condition as deadly as heart attacks or strokes, but far less recognised.

The research group now plans further preclinical studies in larger animal models to test whether this therapy also works in patients already in an advanced stage of sepsis.

Source: VIB (the Flanders Institute for Biotechnology) 

Categories : Emergency MedicineTags :

Statins May Reduce Mortality Risk by 39% for Patients with Septic Shock

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Each year in the US alone, approximately 750 000 patients are hospitalised for sepsis, of which approximately 27% die. In about 15% of cases, sepsis worsens into septic shock, characterised by dangerously low blood pressure and reduced blood flow to tissues. The risk of death from septic shock is even higher, between 30% and 40%.

The earlier patients with sepsis are treated, the better their prospects. Typically, they receive antibiotics, intravenous fluids, and vasopressors to raise blood pressure. But now, a large cohort study in Frontiers in Immunology has shown for the first time that supplementary treatment with statins could boost their chances of survival.

“Our large, matched cohort study found that treatment with statins was associated with a 39% lower death rate for critically ill patients with sepsis, when measured over 28 days after hospital admission,” said Dr Caifeng Li, the study’s corresponding author and an associate professor at Tianjin Medical University General Hospital in China.

Statins are best known as a protective treatment against cardiovascular disease, which function by lowering ‘bad’ LDL cholesterol and triglycerides, and raising ‘good’ HDL cholesterol. But they have been shown to bring a plethora of further benefits, which explains the burgeoning interest in their use as a supplementary therapy for inflammatory disorders, including sepsis.

Not just lowering cholesterol

“Statins have anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic properties. They may help mitigate excessive inflammatory response, restore endothelial function, and show potential antimicrobial activities,” said Li.

The authors sourced their data from the public Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, which holds the anonymised e-health records of 265 000 patients admitted to the emergency department and the intensive care unit of the Beth Israel Deaconess Medical Center of Boston between 2008 and 2019. Only adults with a diagnosis of sepsis hospitalised for longer than 24 hours were included here.

The authors compared outcomes between patients who received or didn’t receive any statins during their stay besides standard of care, regardless of the type of statin. Unlike in randomised clinical trials, the allocation of treatments is not determined by random in observational studies like the present cohort study. This means that it is in principle hard to rule out that an unknown underlying variable affected allocation, for example if physicians unconsciously or on purpose were prone to give statins to those patients most likely to benefit from them.

However, Li and colleagues used a technique called ‘propensity score matching’ to minimize the risk of such bias: they built a statistical model to determine a likelihood score that a given patient would receive statins, based on their medical records, and then found a matching patient with a similar score, but who didn’t receive statins. In the final sample, 6070 critical patients received statins while another 6070 did not.

Source: Frontiers

Categories : AntibioticsTags :

Which is Better? Prolonged vs Intermittent Infusion of β-Lactams in Sepsis

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In adults with sepsis or septic shock, β-lactams are recommended by Surviving Sepsis Campaign guidelines, in a prolonged (after an initial bolus) rather than intermittent infusions – but owing to only moderate quality of evidence this is currently a weak recommendation. Now, a new systematic review and meta-analysis comparing the two approaches across multiple clinical trials has found a survival benefit for prolonged infusion The findings appear in JAMA.

To address whether prolonged infusions of β-lactams improve clinically important outcomes in critically ill adults with sepsis or septic shock, the study investigators searched medical databases for relevant randomised controlled trials comparing β-lactam infusion types in critically ill adults with sepsis or septic shock. The primary outcome was 90-day mortality, with secondary outcomes including intensive care unit (ICU) mortality and clinical cure.

In all, they found 18 eligible trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome.

The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86, with high certainty and a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. There was high certainty that prolonged infusion of β-lactam antibiotics was associated with a reduced risk of ICU mortality (risk ratio, 0.84) and moderate certainty of an increase in clinical cure (risk ratio, 1.16).

The findings were tempered with the authors’ understanding that, “Potential challenges associated with prolonged infusion administration, including drug instability and incompatibility with other intravenous medications, the need for a dedicated intravenous portal, and the potential effect on clinical workload, require some considerations before broad implementation. Future studies should determine the optimal duration of infusion when β-lactam antibiotics are administered as prolonged infusions.”

The authors concluded that, “Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock.”

Categories : Diseases, Syndromes and ConditionsTags :

An ‘Epidemic’ of Sepsis in Southern Sweden

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A research team in Sweden has found that more than 4% of all hospital admissions in southern Sweden, also known as Skåne, are associated with sepsis. The results, published in JAMA Network Open, suggest that is a significantly under-diagnosed condition that can be likened to an epidemic.

In 2016, the researchers conducted an initial study where they revealed that sepsis is much more common than previously believed. The incidence turned out to be 750 adults per 100 000 individuals. In the latest study in the same region, the results showed that more than 4% of all hospitalisations involved the patient suffering from sepsis, and 20% of all sepsis patients died within three months.

“This makes sepsis as common as cancer with similar negative long-term consequences, and as deadly as an acute myocardial infarction. Among sepsis survivors, three-quarters also experience long-term complications such as heart attacks, kidney problems, and cognitive difficulties,” says Adam Linder, sepsis researcher and associate professor at the Departmentof infection medicine at Lund University, as well as a senior physician at Skåne University Hospital.

The European Sepsis Alliance has assigned the researchers with assessing how common sepsis is in the rest of Europe. Given the differing healthcare systems across countries, it wasn’t immediately clear how they should proceed to obtain accurate figures. Consequently, the researchers conducted a pilot study southern Sweden to determine if their methods were applicable to other European hospitals.

“Doctors classify patients using diagnostic codes. Since sepsis is a secondary diagnosis resulting from an infection, the condition is significantly underdiagnosed, as the primary disease often dictates the diagnostic code. This makes it challenging to find a way to accurately determine the number of sepsis cases,” says Lisa Mellhammar, sepsis researcher at Lund University and assistant senior physician at Skåne University Hospital.

The research showed that 7500 patients in southern Sweden were associated with sepsis in 2019, and the incidence increased to 6% during the COVID pandemic. However, even in the absence of COVID, the researchers believe that sepsis should be viewed as an epidemic.

The aim is to use the publication to influence the EU to establish a common surveillance system for sepsis. The team are in contact with authorities and researchers from around thirty European countries and hope that the research project can secure sufficient funding to start soon. There is no indication that the number of sepsis cases would be lower in other parts of Europe than in Sweden. In Swedish hospitals, only two percent of all sepsis patients are antibiotic-resistant, and the researchers speculate that the proportion of resistant cases is higher in many other European countries.

“Although sepsis care has improved in recent years, we need to enhance our diagnostic methods to identify patients earlier and develop alternative treatment methods beyond antibiotics to avoid resistance. Increasing awareness about sepsis among the public and decision-makers is crucial to ensure that resources are allocated appropriately,” concludes Adam Linder.

Source: Lund University

Categories : HospitalsTags :

Which IV Fluids to Use in Sepsis… and When Not to Use Them

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In the leading Journal of the American Medical Association, two researchers outline how to use intravenous fluids to treat sepsis, a deadly condition that affects nearly a third of all ICU patients. Despite the fact that IV fluid therapy is a cornerstone of sepsis treatment, it’s not always a sure bet – in fact, as the authors outline in their paper, giving IV fluids can sometimes worsen sepsis.

Which fluids to give, how much to give and when have been fiercely debated for years.  

“This is an intervention that is cheap and easy to use and it can be life-saving, but it can also be harmful for patients if too much fluid is given,” explains first author Fernando Zampieri, a newly recruited assistant professor at University of Alberta.    

The new JAMA article sums up the latest science on the phases of sepsis and how much IV fluid to give at each stage of treatment. 

“It’s aimed at the clinician who works on the wards, who works in community hospitals, who works in emergency departments, explaining the mechanisms to assess whether patients are responding or not and decide whether more fluid needs to be given,” says Sean Bagshaw, professor and chair of critical care medicine, who co-wrote the paper with Zampieri and Matthew Semler of Vanderbilt University.

“These are really fundamental issues that have been challenging for clinicians to reconcile and have long been controversial, so this concise review bundles all recent evidence together,” Bagshaw says.

A complex and life-threatening condition

One in four patients who develop sepsis die from it, and it’s responsible for 11 million deaths per year, Zampieri estimates. Sepsis is an extreme response by the body to an infection, leading to a drop in blood pressure and thus a lack of oxygen circulation. Death occurs when oxygen-deprived organs such as the brain, kidneys or liver fail. 

Treatment almost always includes administering intravenous fluids, along with other interventions such as antibiotics and medications to boost blood pressure and oxygen delivery to tissues. The goal is to restore circulation without causing edema, or swelling, which can also be harmful to organs. 

Sepsis can occur at any time in life from infancy to old age, says Bagshaw. Zampieri points out that sepsis is not really one disease, but a complex condition with multiple causes. 

“When we talk about sepsis, you can be talking about things as different as a young woman with an infection after delivery all the way through to an elderly patient with a urinary tract infection. Those are two completely separate sources of infection, and the patient’s other conditions make treatment more complicated,” he says.

Zampieri says there are numerous clinical trials underway to refine sepsis treatment, but much is still unknown. Zampieri himself has been involved with trials in Brazil to determine whether slower fluids make a difference to clinical outcomes, to compare the efficacy of using saline versus a balanced solution (Plasma-Lyte 148), and to find out whether measuring lactic acid, which is produced when the body is starved of oxygen, is a good indicator of whether enough fluids have been given.

Digging for evidence to improve practice

Zampieri plans to continue his program of clinical trials and also wants to help physicians and health systems adopt best treatment practices as they are verified. Eventually he hopes to develop an accurate bedside test, such as using ultrasound, to better determine what level of fluids a patient requires.  

“Clinical trials are the best way to provide evidence that will change practice,” he says.

Bagshaw expects sepsis treatment to improve rapidly over the next decade thanks to such work.

“It took us 30 or 40 years to get to this point, and I think there’s still lots of questions to be answered about how best to individualise the resuscitation strategies amongst patients with life-threatening infection and sepsis,” Bagshaw says. “My hope is that Fernando will help catalyse some of those advances here at the U of A.”

Source: University of Alberta