Drugs that cool brain can save patients before they reach A&E
Pills that plunge the body and brain into hypothermia could reduce disability and deaths from strokes.
People who have a cardiac arrest, where the heart suddenly stops beating properly, depriving the brain of blood and oxygen; or who damage their spinal cord in a car crash, could also benefit from a form of the treatment with everyday tablets – paracetamol, aspirin or ibuprofen.
Ideally, paramedics will administer the drugs when they arrive on the scene. As Samir Ayoub, a senior lecturer in pharmacology at the University of East London, who has been investigating this approach, explains: ‘Our end goal is that critically ill patients receive drug-induced hypothermia before they even get to hospital because the first hour when someone is in cardiac arrest, spinal injury or stroke is crucial.
‘We know that patients need to be cooled down quickly to have the best chance of a good outcome.’
The idea of using hypothermia to help the body heal isn’t new.
Therapeutic hypothermia – lowering the body temperature from around 37C to between 33-34C for 12 to 24 hours – is widely used to treat traumatic head injuries, spinal cord injuries, cardiac arrests, as well as for newborns who have been deprived of oxygen at birth.
It slows the brain’s metabolic rate, reduces inflammation and stops brain cells dying – increasing the chance of a full recovery.
Samir Ayoub, a senior lecturer in pharmacology at the University of East London, believes that cocktails of drugs may be needed to cool the body enough for hypothermia to set in
But current cooling techniques involve placing cooling bags directly on the skin or infusing cold saline solution straight into the patient’s bloodstream.
This means they can only be performed in hospital, potentially costing valuable time during the so-called ‘golden hour’, the period when treatment for patients who have had a stroke, for example, means they are much more likely to avoid long-term disability. Early treatment of strokes also increases the odds of survival.
A new study involved two medicines that have been safely used since the 1950s to treat other conditions.
Scientists at Capital Medical University in Beijing showed that, when administered together, chlorpromazine (normally used for schizophrenia and severe nausea) and promethazine (typically given for allergies and nausea) significantly lowered the body temperature of mice and primates.
Crucially, the combination also reduced damage to the brain after a stroke.
The researchers followed this up with a clinical trial involving 32 people who had just had ischaemic strokes – where a clot travels to the brain and blocks its blood supply.
At the highest dose, body temperature dropped around 1C. However, the reduction was small and not enough to trigger hypothermia as it had in mice and primates.
This may be because humans have a lower surface area to body mass ratio – meaning they have a relatively small amount of skin compared to their weight – which means it takes heat longer to dissipate through the skin.
Therapeutic hypothermia slows the brain’s metabolic rate, reduces inflammation and stops brain cells dying, which can increase the chance of a full recovery
‘How it works is still not completely understood but therapeutic hypothermia almost certainly protects the brain from further damage,’ David Baker, an emeritus professor of neuroimmunology at Queen Mary University of London, told Good Health.
One theory is that the drugs act on the thermostat in the brain to prevent shivering, the body’s way of warming itself up – this is something that cooling bags and saline solutions do not curb.
Professor Baker adds: ‘Drug-induced hypothermia may be preferable to physical cooling because the body is programmed to resist cold, and shivering is a process to create heat. Inside-out cooling [with drugs] would stop these mechanisms.’ Drugs may also widen blood vessels to release heat and reduce the metabolic rate – the burning of energy.
The downside of physical cooling is that it can trigger a spike in stress hormones, a slow heart rate, low blood pressure and changes to white blood cells that increase the risk of infections. It can interfere with blood’s ability to clot too, which makes bleeds more likely.
The hope is that the inside-out treatment will help with this too.
Meanwhile, other researchers are looking at whether household medicines used for fevers, such as paracetamol, aspirin and ibuprofen, could also cool the body rapidly when needed. Paracetamol can lower body temperature by as much as 1C for up to four hours at a time, research by Samir Ayoub found.
In a review he published in the journal Temperature in 2021, he concluded it was because the popular painkiller blocks an enzyme called COX-1, which is involved in producing prostaglandins – hormones responsible for raising the body’s temperature.
Samir Ayoub believes that cocktails of drugs may be needed to cool the body enough for hypothermia to set in.
In addition, ‘if you only used one drug, you would have to give such a high dose that it might end up having a detrimental effect’, he says. ‘We know higher doses of drugs can induce toxicity even if it is only short term. For example, paracetamol can cause liver damage if given beyond the recommended therapeutic dose.’
Other experts caution that there is a long way to go.
The scientists in China only lowered human body temperature by less than 1C, ‘too small to achieve a sufficient cooling effect’, said Malcolm Macleod, a professor of neurology and translational neuroscience at the University of Edinburgh. ‘The prospects of this doing anything are low indeed.’
