How to use NSAIDS to treat Sepsis
Sepsis is a complex and hard-to-define condition with many different interactions with other disorders. Presently, there are no estimates of the burden of sepsis and septicaemia at the global level and how to treat sepsis using ibuprofen and aspirin.
A potentially life-saving treatment for sepsis has been under our noses for decades in the non-steroidal anti-inflammatory drugs (NSAIDs) most people have in their medicine cabinets, a new University of Colorado Boulder study suggests.
Sepsis Fact Sheet
Septicaemia, also known as sepsis, is a rare but serious complication of an infection that can quickly lead to multiple organ failure and death.
The blood poisoning occurs when large amounts of bacteria enter the bloodstream.
Bacterial meningitis can lead to septicaemia.
Sepsis can also be caused by viral or fungal infections, although bacterial infections are by far the most common cause.
Symptoms in children under 5
- your child may look mottled, bluish or pale
- is very lethargic and difficult to wake
- feels abnormally cold to touch
- is breathing very fast or having difficulty breathing
- has a rash that does not fade when you press on it
- is fitting or convulsing
- has a high temperature
- refusing to eat or drink
- has not had a wee for over 12 hours
Symptoms in older children and adults
- a high temperature
- chills and shivering
- fast heartbeat
- fast breathing
- feeling dizzy or faint
- confusion and disorientation
- nausea and vomiting
- slurred speech
- severe muscle pain
- not urinating for a day
- cold, clammy and pale skin
- loss of consciousness
If any of these symptoms develop you should seek medical advice straight away.
Each year more than 1.3 million people in the Nigeria contract sepsis, an overwhelming immune response to infection.
It kills as many as half of those who contract it, sometimes within day.
As the number of cases rises, particularly in intensive care units, pharmaceutical companies have been scrambling to develop a drug to combat the condition.
“NSAIDS like ibuprofen and aspirin are among the most prevalent pharmaceuticals worldwide, with over 30 billion doses taken annually in the United States alone.”
HOW TO TREAT SEPSIS USING IBUPROFEN AND ASPIRIN
“But their precise mechanisms of action are not entirely understood,” said Hang Hubert Yin, a biochemistry professor at CU Boulder’s BioFrontiers Institute and lead author of the new paper, published today in Cell Chemical Biology.
“We provide the first evidence for a novel mechanism of action for NSAIDS, one we believe could have a direct impact on people’s lives.”
Researchers have long known that NSAIDs work in part by inhibiting an enzyme called cyclooxygenase (COX). They’ve also known that these NSAIDs can come with serious side effects.
Some NSAIDs have been removed from the market after showing they boosted risk of heart attack and stroke.
But Yin’s research found that a subgroup of NSAIDs also act strongly and independently on another family of enzymes, caspases, which reside deep within the cell and have recently been found to play a key role in aggressive immune responses, like sepsis.
“For instance, some chemicals derived from bacteria actually penetrate the cell and trigger the caspase response, prompting the cell to commit suicide. This also is known as apoptosis,” said Yin. “Such activation, in turn, potentially causes inflammation.”
After the disappointing failure of late-stage clinical trials of anti-sepsis drugs targeting an immune receptor called toll-like receptor 4 (TLR4), located on the surface of cells, Yin and other scientists began to wonder if the key to halting the disease was to develop an antiseptic therapy that simultaneously targets caspases.
As a first step, his team screened 1,280 existing FDA-approved drugs for caspase-inhibiting activity. Of the 27 that lit up, half were NSAIDs. NSAIDs also comprised eight of the top 10 most potent caspase inhibitors.
HOW TO TREAT SEPSIS USING IBUPROFEN AND ASPIRIN
“It was a complete surprise,” said Yin.
He and study co-author Ding Xue, a professor in the department of Molecular Cellular and Developmental Biology, then used biochemical and biophysical assays in the lab, as well as experiments with roundworms to test the theory further.
“We showed that NSAIDs were effective in delaying cell death in worms, presumably by blocking caspase activity.”
It remains questionable whether existing NSAIDs, perhaps in higher doses, could be used to treat sepsis. The risk of side effects may be too great, said Yin.
But he is already working on follow-up studies looking at whether new sepsis drugs could be developed combining caspase-inhibiting NSAIDS and TLR4 inhibitors.
NSAIDs could also potentially be repurposed to address other conditions, including rheumatoid arthritis and neuro-degenerative diseases.
“To think about the wide potential applications of these NSAID drugs is very exciting,” Yin said.
He hopes the research will also help scientists better understand why NSAIDs cause serious side effects like liver, kidney and cardiovascular problems, so they can develop safer next-generations versions.
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