Tag: anaesthesia

Categories : NeurologyTags :

Under Different Anaesthetics, Same Result: Unconsciousness by Shifting Brainwave Phase

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MIT study finds that an easily measurable brain wave shift may be a universal marker of unconsciousness under anaesthesia

Photo by Anna Shvets on Pexels

At the level of molecules and cells, ketamine and dexmedetomidine work very differently, but in the operating room, they do the same exact thing: anaesthetise the patient. By demonstrating how these distinct drugs achieve the same result, a new study in animals by neuroscientists at The Picower Institute for Learning and Memory at MIT identifies a potential signature of unconsciousness that is readily measurable to improve anaesthesiology care.

What the two drugs have in common, the researchers discovered, is the way they push around brain waves, which are produced by the collective electrical activity of neurons. When brain waves are in phase, meaning the peaks and valleys of the waves are aligned, local groups of neurons in the brain’s cortex can share information to produce conscious cognitive functions such as attention, perception and reasoning, said Picower Professor Earl K. Miller, senior author of the new study in Cell Reports. When brain waves fall out of phase, local communications, and therefore functions, fall apart, producing unconsciousness.

The finding, led by graduate student Alexandra Bardon, not only adds to scientists’ understanding of the dividing line between consciousness and unconsciousness, Miller said, but also could provide a common new measure for anesthesiologists who use a variety of different anesthetics to maintain patients on the proper side of that line during surgery.

“If you look at the way phase is shifted in our recordings, you can barely tell which drug it was,” said Miller, a faculty member in The Picower Institute and MIT’s Department of Brain and Cognitive Sciences. “That’s valuable for medical practice.  Plus if unconsciousness has a universal signature, it could also reveal the mechanisms that generate consciousness.”

A figure from the paper summarises the main findings. Under either ketamine or dexmedetomidine general anaesthesia, brain waves become shifted out of phase within a hemisphere and more into phase across hemispheres.

If more anesthetic drugs are also shown to affect phase in the same way, then anaesthesiologists might be able to use brain wave phase alignment as a reliable marker of unconsciousness as they titrate doses of anesthetic drugs, Miller said, regardless of which particular mix of drugs they are using. That insight could aid efforts to build closed-loop systems that can aid anaesthesiologists by constantly adjusting drug dose based on brain wave measurements of the patient’s unconsciousness.

Miller has been collaborating with study co-author Emery N. Brown, an anaesthesiologist and Professor of Computational Neuroscience and Medical Engineering, on building such a system. In a recent clinical trial with colleagues in Japan, Brown demonstrated that monitoring brain wave power signals using EEG enabled an anaesthesiologist to use much less sevoflurane during surgery with young children. The reduced doses proved safe and were associated with many improved clinical outcomes, including a reduced incidence of post-operative delirium.

Phase findings

Neuroscientists studying anaesthesia have rarely paid attention to phase, but in the new study, Bardon, Brown and Miller’s team made a point of it as they anaesthetised two animals.

After the animals lost consciousness, the measurements indicated a substantial increase in “phase locking,” especially at low frequencies. Phase locking means that the relative differences in phase remained more stable. But what caught the researchers’ attention were the differences that became locked in: Within each hemisphere, regardless of which anesthetic they used, brain wave phase became misaligned between the dorsolateral and ventrolateral regions of the prefrontal cortex.

Surprisingly, brain wave phase across hemispheres became more aligned, not less. But Miller notes that case is still a big shift from the conscious state, in which brain hemispheres are typically not aligned well, so the finding is a further indication that major changes of phase alignment, albeit in different ways at different distances, are a correlate of unconsciousness compared to wakefulness.

“The increase in interhemispheric alignment of activity by anesthetics seems to reverse the pattern observed in the awake, cognitively engaged brain,” the Bardon and Miller team wrote in Cell Reports.

Determined by distance

Distance proved to be a major factor in determining the change in phase alignment. Even across the 2.5 millimetres of a single electrode array, low-frequency waves moved 20-30 degrees out of alignment. Across the 20 or so millimetres between arrays in the upper (dorsolateral) and lower (ventrolateral) regions within a hemisphere, that would mean a roughly 180-degree shift in phase alignment, which is a complete offset of the waves.

The dependence on distance is consistent with the idea of waves traveling across the cortex, Miller said. Indeed in a 2022 study, Miller and Brown’s labs showed that the anaesthetic propofol induced a powerful low-frequency traveling wave that swept straight across the cortex, overwhelming higher-frequency straight and rotating waves.

The new results raise many opportunities for follow-up studies, Miller said. Does propofol also produce this signature of changed phase alignment? What role do travelling waves play in the phenomenon? And given that sleep is also characterised by increased power in slow wave frequencies, but is definitely not the same state as anaesthesia-induced unconsciousness, could phase alignment explain the difference?

Source: Picower Institute

Categories : NeurologyTags :

Anaesthesia Experiment Hints at Consciousness Arising from Quantum Effects

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Photo by Bruce Christianson on Unsplash

For decades, one of the most fundamental and vexing questions in neuroscience has been: what is the physical basis of consciousness in the brain? Most researchers favour classical models, based on classical physics, while a minority have argued that consciousness must be quantum in nature, and that its brain basis is a collective quantum vibration of ‘microtubule’ proteins inside neurons.

New research from Wellesley College published in eNeuro has yielded important experimental results relevant to this debate, by examining how anaesthesia affects the brain of rat models. Volatile anaesthetics are currently believed to cause unconsciousness by acting on one or more molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins.

Anaesthetic gases including isoflurane bind to cytoskeletal microtubules (MTs) and dampen their quantum optical effects, potentially contributing to causing unconsciousness. This idea is supported by the observation that taxane chemotherapy, consisting of MT-stabilising drugs, reduces anaesthesia effectiveness during surgery in human cancer patients.

Lead researcher professor Mike Wiest and his research team found that when they gave rats the brain-penetrant MT–stabilising drug epothilone B (epoB), it took the rats significantly longer (69s) to fall unconscious under 4% isoflurane, as measured by loss of righting reflex (LORR).

The effect could not be accounted for by tolerance from repeated exposure to isoflurane.

Their results suggest that binding of the anesthetic gas isoflurane to MTs causes unconsciousness and loss of purposeful behaviour in rats (and presumably humans and other animals). This supports the idea that consciousness is a quantum state tied to MTs.

“Since we don’t know of another (ie, classical) way that anesthetic binding to microtubules would generally reduce brain activity and cause unconsciousness,” Wiest says, “this finding supports the quantum model of consciousness.”

It’s hard to overstate the significance of the classical/quantum debate about consciousness, says Wiest, an associate professor of neuroscience at Wellesley. “When it becomes accepted that the mind is a quantum phenomenon, we will have entered a new era in our understanding of what we are,” he says. The new approach “would lead to improved understanding of how anaesthesia works, and it would shape our thinking about a wide variety of related questions, such as whether coma patients or non-human animals are conscious, how mysterious drugs like lithium modulate conscious experience to stabilize mood, how diseases like Alzheimer’s or schizophrenia affect perception and memory, and so on.”

More broadly, a quantum understanding of consciousness “gives us a world picture in which we can be connected to the universe in a more natural and holistic way,” Wiest says. Wiest plans to pursue future research in this field, and hopes to explain and explore the quantum consciousness theory in a book for a general audience.

Source: Wellesley College

Categories : Pain ManagementTags :

Brain Structures Predict Risk of Awareness under Anaesthesia

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Photo by Anna Shvets on Pexels

Awareness during anaesthesia is an extremely rare but horrific risk for patients. Now, for the first time, neuroscientists have identified brain structures which could predict an individual’s predisposition this phenomenon. The findings, just published in the journal Human Brain Mapping, could help identify patients who need larger anaesthetic doses.

Although anaesthesia has been used in clinical medicine for over 150 years, scientists do not fully understand why its effect on people is so varied. One in four patients presumed to be unconscious during general anaesthesia may in fact have subjective experiences, such as dreaming. Estimated to occur in 1:1000 to 1:20 000 cases, some patients may have awareness under general anaesthetic. These experiences may range from hearing sounds to the pain of surgery combined with the sensation of suffocation and paralysis in the setting of neuromuscular blockade.

The researchers from Trinity College Dublin found that one in three participants were unaffected by moderate propofol sedation in their response times, thus thwarting a key aim of anaesthesia – the suppression of behavioural responsiveness.

The research also showed, for the first time, that the participants who were resistant to anaesthesia had fundamental differences in the function and structures of the fronto-parietal regions of the brain to those who remained fully unconscious. Crucially, these brain differences could be predicted prior to sedation.

Lorina Naci, Associate Professor of Psychology, Trinity who lead the research said:

“The detection of a person’s responsiveness to anaesthesia prior to sedation has important implications for patient safety and wellbeing. Our results highlight new markers for improving the monitoring of awareness during clinical anaesthesia. Although rare, accidental awareness during an operation can be very traumatic and lead to negative long-term health outcomes, such as post-traumatic stress disorder, as well as clinical depression or phobias.”

“Our results suggest that individuals with larger grey matter volume in the frontal regions and stronger functional connectivity within fronto-parietal brain networks, may require higher doses of propofol to become nonresponsive compared to individuals with weaker connectivity and smaller grey matter volume in these regions.”

The research, conducted in Ireland and Canada, investigated 17 healthy individuals who were sedated with propofol, the most common clinical anaesthetic agent. The participants’ response time to detect a simple sound was measured when they were awake and as they became sedated. Brain activity of 25 participants as they listened to a simple story in both states was also measured.

Source: Trinity College Dublin

Categories : Obstetrics & Gynaecology Pain ManagementTags :

Study Finds No Adverse Effects Denying Nitrous Oxide in Labour

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Photo by Jonathan Borba on Unsplash

Birthing women denied nitrous oxide(N20) to relieve labour pain as a result of the COVID pandemic received opioids instead, without any adverse outcomes for mother or child, according to a new study published in the Australian and New Zealand Journal of Obstetrics and Gynaecology. Some anaesthetists have also argued for reducing N20 use as it is a greenhouse gas.

The study, conducted at Lyell McEwin Hospital in Australia, looked at the impact of withholding nitrous oxide (N20), a decision adopted by many hospitals worldwide over fears of virus transmission from the aerosol-generating procedure.

Anaesthetist Professor Bernd Froessler and colleagues compared patient notes for all 243 women birthing at Lyell McEwin over a seven week period in March/April 2020, half of whom did not have access to N20.

They found that although opioid use “significantly increased” when N20 was withheld, there was no increase in epidural use and no change in labour duration, Caesarean section rates, birthing complications or newborn alertness.

Nitrous oxide is used by more than 50% of Australian women to relieve pain in labour, followed by epidurals (40%) and opioids (12%), according to the Australian Institute of Health and Welfare.

However, N20 represents 6% of global greenhouse gas emissions, with 1% due to medical use (ie, around 0.06% of total global warming is due to medical N20). This has led to a debate in medical circles whether it should be replaced with other methods of pain relief.

Many obstetricians argue that effective pain relief in childbirth should be the priority, particularly given the low percentage of emissions, but the Australian and New Zealand College of Anaesthetists has advocated for a reduction in N20 use in a bid to improve environmental sustainability in anaesthesia.

“Obviously no-one wants to deprive labouring women of adequate and easy pain relief but given there are other analgesic options, including epidurals and opioids, perhaps these could be considered,” said Prof Froessler.

UniSA statistician and researcher Dr Lan Kelly said that the findings should reassure women that pain relief besides N20 does not compromise their health or their baby’s.

However, in a recent Sydney Morning Herald article, principal midwifery officer at the Australian College of Midwives, Kellie Wilton, said mothers should not be made to feel guilty about their pain relief choices and suggested hospitals could introduce nitrous oxide destruction systems to allow for its ongoing use.

When nitrous oxide destruction systems were introduced in Swedish hospitals, the carbon footprint from the gas was halved.

Source: University of South Australia

Categories : NeurologyTags :

MRI Unveils Secrets of Brains under Anaesthesia

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Depiction of a human brain
Image by Fakurian Design on Unsplash

A study published in eLife reveals how the brains of humans and other primates under anaesthesia differ from mammals such as mice, with the visual cortex in primates being isolated from certain effects.

Anaesthesia still holds mysteries for modern science. Electroencephalography (EEG) studies show that, during anaesthesia, the brain is put into a deep sleep-like state in which periods of rhythmic electrical activity alternate with periods of complete inactivity. This state is called burst-suppression. Until now, it was unclear where exactly this state happens in the brain and which brain areas are involved.

Shedding light on the phenomenon would help better understand how the brain functions under anaesthesia. To this end, researchers used functional magnetic resonance imaging (fMRI) to study the precise spatial distribution of synchronously working brain regions in anaesthetised humans, long-tailed macaques, common marmosets and rats. They were able to show for the first time that the areas where burst-suppression is evident differ significantly in primates and rodents. While in rats large parts of the cerebral cortex synchronously show the burst-suppression pattern, in primates individual sensory regions, such as the visual cortex, are excluded from it.

“Our brain can be thought of as a full soccer stadium when we are awake,” explained Nikoloz Sirmpilatze, lead author of the study. “Our active neurons are like tens of thousands of spectators all talking at once. Under anaesthesia, however, neuronal activity is synchronised. You can measure this activity using EEG as uniform waves, as if all the spectators in the stadium were singing the same song. In deep anaesthesia, this song is repeatedly interrupted by periods of silence. This is called burst-suppression. The deeper the anaesthesia, the shorter the phases of uniform activity, the bursts, and the longer the periodically recurring inactive phases, the so-called suppressions.”

The phenomenon is caused by many different anaesthetics, some of which vary in their mechanisms of action. And burst-suppression is also detectable in coma patients. However, it is not known whether this condition is a protective reaction of the brain or a sign of impaired functioning. It has also been unclear where in the brain burst-suppression occurs and which brain areas are involved, as localisation by EEG alone is not possible.

To answer this question, the researchers fMRI. In the first part of the study, the researchers established a system to evaluate fMRI data in humans, monkeys and rodents in a standardised manner using the same method. To do this, they used simultaneously-measured EEG and fMRI data from anaesthetised patients that had been generated in a previous study. “We first looked to see whether the burst-suppression detected in the EEG was also visible in the fMRI data and whether it showed a certain pattern,” says Nikoloz Sirmpilatze. “Based on that, we developed a new algorithm that allowed detecting burst-suppression events in the experimental animals using fMRI, without additional EEG measurement.”

The researchers then performed fMRI measurements in anaesthetised long-tailed macaques, common marmosets and rats. In all animals, they were able to detect and precisely localise burst-suppression as a function of anesthetic concentration. The spatial distribution of burst-suppression showed that in both humans and monkey species, certain sensory areas, such as the visual cortex, were excluded from it. In contrast, in the rats, the entire cerebral cortex was affected by burst-suppression.

“At the moment, we can only speculate about the reasons,” said Nikoloz Sirmpilatze, who was awarded the German Primate Center’s 2021 PhD Thesis Award for his work. “Primates orient themselves mainly through their sense of sight. Therefore, the visual cortex is a highly specialised region that differs from other brain areas by special cell types and structures. In rats, this is not the case. In future studies, we will investigate what exactly happens in these regions during anaesthesia to ultimately understand why burst-suppression is not detectable there with fMRI.”

Susann Boretius, senior author of the study adds: “The study not only raises the question of the extent to which rodents are suitable models for many areas of human brain research, especially when it comes to anaesthesia, but the results also have many implications for neuroscience and the evolution of neural networks in general.”

Source: Deutsches Primatenzentrum (DPZ)/German Primate Center

Categories : HospitalsTags :

Equivalent Hip Surgery Outcomes for Spinal vs General Anaesthesia

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Research comparing general versus spinal anaesthesia for hip fracture surgery shows similar outcomes for patients, challenging the common thinking that patients receiving spinal anaesthesia fare better. 

Led by researchers from the Perelman School of Medicine at the University of Pennsylvania, the study was published in the New England Journal of Medicine and presented at Anesthesiology 2021, the annual meeting of the American Society of Anesthesiologists (ASA).

“Available evidence has not definitively addressed the question of whether spinal anaesthesia is safer than general anaesthesia for hip fracture surgery, an important question to clinicians, patients, and families. Our study argues that, in many cases, either form of anaesthesia appears to be safe,” said lead investigator Mark D. Neuman, MD, MSc, an associate professor of Anesthesiology and Critical Care. “This is important because it suggests that choices can be guided by patient preference rather than anticipated differences in outcomes in many cases.”

While most of the 250 000 annual hip fracture patients in the US undergo general anaesthesia, spinal anaesthesia increased by 50% between 2007 and 2017, while in the United Kingdom and other countries, spinal anaesthesia is used in over 50% of hip fracture cases. [PDF]

Most recent comparisons of general anaesthesia versus spinal anaesthesia come from non-randomised studies, some indicating fewer cognitive and medical complications with spinal. Some patients may choose spinal anaesthesia for lower complications, while those choosing general may have a fear of spinal injection or insufficient anaesthesia. 

The study enrolled 1600 patients, all at least 50 years old, who had broken a hip. Among older populations, hip fractures are particularly worrisome as they can lead to a loss of mobility, linked to a doubling or even tripling the risk of near-term death. The patients were randomised into two groups, a major advantage for the study.

The researchers combined subsequent patient death rates and whether they regained the ability to walk, even with a walker. By 60 days post-surgery, 18.5% of patients assigned to spinal anaesthesia had either died or become newly unable to walk versus 18% of patients who received general anaesthesia. Mortality at this point was 3.9% of patients who received spinal anaesthesia died versus 4.1% who got general anaesthesia.

Additionally, to examine how the different forms of anaesthesia factored into potential cognitive complications, the researchers also examined post-operative delirium. Delirium was experienced in 21% of spinal anaesthesia patients versus 20% for general anaesthesia.

“What our study offers is reassurance that general anaesthesia can represent a safe option for hip fracture surgery for many patients,” said Prof Neuman. “This is information that patients, families, and clinicians can use together to make the right choice for each patient’s personalised care.”

Source: Perelman School of Medicine at the University of Pennsylvania