Sedative may prevent delirium after operation with general anaesthetic

A mild sedative could greatly reduce the risk of people experiencing delirium after an operation with general anaesthetic, according to new research.

The study, by scientists at Imperial College London and Peking University First Hospital, suggests sedating patients after they undergo an operation may reduce the risk of post-operative delirium by up to 65%.

The condition may affect up to one in three people who have a major operation, causing confusion and hallucinations – with the over-65s particularly at risk.

The team, who published their study in The Lancet, believe the sedative may help the brain ‘recover and reset’ after surgery.

Post-operative delirium usually strikes within the first two days of a person waking from general anaesthetic.

The symptoms range from relatively mild, such as a person not knowing their name or where they are, to more severe, such as aggressive behaviour, believing people are trying to harm them, or even hallucinations.

Professor Daqing Ma, co-lead author of the study from the Department of Surgery and Cancer at Imperial College London, said: “Post-operative delirium is a huge challenge for the medical community – and incredibly distressing for patients and their families. In many cases patients become almost child-like, and do not understand where they are, what is happening, and become very upset. Hospital staff have also been injured by delirious patients becoming aggressive. However, we currently have no treatment options available for this condition.”

The causes are unknown, but one theory is that major surgery can trigger inflammation throughout the body, which in some cases can spread to the brain.

The risk of the condition increases with age, and it seems to strike more often when patients undergo major, lengthy operations.

The delirium can last from a few hours to a couple of days, and some research suggests it may be linked to an increased risk of elderly patients later developing dementia.

In the study, co-led by Professor Dongxin Wang at Peking University First Hospital, researchers assessed 700 patients age 65 or older who were about to undergo major surgery at the Beijing hospital.

Half received a low dose of a type of sedative called dexmedetomidine after the operation, as an infusion directly into a vein in their arm, while half received a placebo salt-water infusion.

The patients received the infusion of sedative or placebo around an hour after surgery, and for the next 16 hours.

This sedative, which is commonly used for medical procedures and in veterinary medicine, leaves a patient relaxed and drowsy, yet conscious. The drug is considered safe as it doesn’t affect breathing.

Both groups received the same general anaesthetic before undergoing their operation. They were then assessed forsymptoms of delirium every day for a week after their procedure.

The results revealed that nearly one in four patients in the placebo group – 23% – developed delirium. However only just under one in ten patients – 9% – who received the sedative developed the condition. Scientists are still unsure how the sedative works, but one theory is it allows the brain to rest and recover immediately after surgery, explained Professor Ma.

“Previous studies have shown that patients who struggle to sleep after their operation – perhaps because they are in pain or on a busy, noisy ward – are at increased risk of delirium.”

He added that the sedative dexmedetomidine seems to not only trigger sleep, but actually mimics the natural state the brain enters during sleep.

“Although other sedatives induce sleep, they do not trigger the natural ‘sleep state’ the brain requires to rest, reset, and recover.”

Professor Ma added that previous research has suggested the sedative may help prevent delirium, but this is the largest study to show such beneficial effects. The study also confirmed there were no side effects of the sedative.

Further results showed the patients given the sedative had fewer post-operative complications than the placebo group, and were discharged from hospital earlier.

The team will now assess if the sedative has long-term benefits, beyond the sevenday study period.

Professor Ma added: “There is still much more work to do around post-operative delirium, as we still don’t fully understand what is happening in the brain, and why some patients are more at risk.

“However, these findings suggest this sedative may be a potential method of preventing post-operative delirium in some patients.”

The research was funded by the Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation.

  • doi: 10.1016/S0140-6736(16)30580-3

CASE STUDY: “I thought I was sailing down the River Trent on a hospital ship.”

Professor Michael Wang, a clinical psychologist from the University of Leicester, suffered post-operative delirium after major heart surgery in 2012. He recalls the experience.

I first woke around 18 hours after my operation at a Leicester hospital. A doctor was speaking with a nurse about my operation at the foot of my bed, and I asked them where we were. I thought the doctor replied Nottingham, which confused me as I thought we were in Leicester.

I formed the conclusion I was on a hospital ship, sailing down the River Trent. My operation took place over the Christmas period, and I thought perhaps the ship was a private facility allowing surgeons and anaesthetists to earn extra money.

I looked out of the window and saw trees moving past on the ‘river bank’, which confirmed my suspicion. I also thought I heard the sound of other ships’ fog horns in the distance, which I now realise was the sound of other patients’ bedside call buttons.

I kept trying to pull out the tubes in my arm and chest, which were providing vital fluid, antibiotics and monitoring as I didn’t believe I needed them.

The staff, who were incredibly patient and to whom I subsequently apologised – said to me: ‘We know you believe this is all part of a conspiracy, but if you pull out your lines you will die.’

Shortly after this, I believed I was moved into a dark room filled with rolled-up carpets. This, of course, didn’t happen and I now know I stayed in my bed on the intensive care unit the whole time.

However, I was convinced I had been placed in this room, and when friends came to visit, I was puzzled by why they needed to squeeze through the gaps between the carpet rolls. I also saw a nurse nearby keeping an eye on me, perched among the rolls of carpet.

Later I awoke to find myself in a sinister Chinese mausoleum under the intensive care unit (or so I thought). It felt like some kind of nightmare, with dark recesses and glowing Chinese symbols. I have since realised these symbols were based on the illuminated heart monitor buttons on the wall opposite my bed.

Once I was discharged from intensive care (approximately three days after my operation) most of the delusions cleared.

Although my hallucinations sound frightening, I felt strangely detached from them. I think this is because of my familiarity, through my work, with the intensive care unit environment and the experiences of patients – and so part of me knew I was suffering from delusions. Indeed, I have researched post-operative delirium and I know that most patients find their experiences far more terrifying than I found mine.

However, the experience allowed me a crucial insight into what patients experience in post-operative delirium, and why it’s so important to gain understanding to improve treatment and prevention of this condition.

Paving the way to safer anaesthesia

Researchers have made a breakthrough which could help prevent patients suffering stress to the body and from feeling pain or becoming aware during anaesthesia.

The breakthrough could help to provide a new guide for anaesthetists and lead to much quicker recovery times for patients following operations as greater optimisation of dosage could lead to drugs being significantly reduced.

If drug levels are judged incorrectly this has led to well documented, albeit very rare, cases of patients becoming aware or feeling pain during surgery due to insufficient dose of anaesthetic drugs. Also, overdosing of drugs may be harmful, resulting in cardiovascular malfunction and prolonged delay in awakening after surgery.

In a study published in the journal Anaesthesia (9 September 2015) researchers tested a new more nuanced form of investigating the subtle clues sent out by the human body during anaesthesia – particularly the cardiovascular signals that can indicate the state of the pain-monitoring autonomous nervous system. The results have proved more reliable than existing methods.

The journal article – The Discriminatory value of Cardiorespiratory Interactions in distinguishing awake from anaesthetised states: A randomised observational study – found that by looking at how key indicators – such as ECG, respiration, skin temperature, pulse and skin conductivity – interacted with one another researchers could much more accurately predict whether a patient was awake or anaesthetised. They also helped distinguish between the effects of two commonly-used anaesthetic drugs, propofol and sevoflurane.

The study measured the depth of anaesthesia of 27 patients in good health during surgery in the United Kingdom and in Norway. Readings were taken at a high frequency – several hundred samples per heart beat – for 30 minutes while the patients were awake before their surgery and for up to 30 minutes during general anaesthesia. The signals showed, with a high degree of accuracy, how the patients reacted to the anaesthetics.

Lancaster University’s Professor Aneta Stefanovska said: “We have developed new methods to study complex interactions between ever changing processes such as the processes in our heart, lungs and vasculature. These physiological processes constantly interact with one another, but anaesthetic drugs change the level of these interactions. By applying our new methods, in this study we were able to get a very accurate picture of what was going on, leading to the most reliable predictions of the state of anaesthesia obtained from cardiovascular signals to date of closer to 97%.”

Johan Raeder, Professor in Anaesthesiology at Oslo University Hospital, who also took part in the study, said: “This very complex work is a logical step further in the search for specific and sensitive methods of objectively detecting the state of anaesthesia.

“While so far, most methods have relied on a single kind of measurement, our work tries to integrate information from many different physiological processes at the same time, thus adding an entirely new perspective. Namely how the different processes interact with each other and synchronise.”

Professor Peter McClintock, also of Lancaster University said: “The likelihood of waking up during surgery is extremely small but, if it happened, it could be a distressing experience. So, we are delighted to pave the way to a new tool for gauging depth of anaesthesia.”

The collaborative research involved consultant anaesthetists from University Hospitals of Morecambe Bay NHS Trust in North West England.

Professor Andrew Smith, Consultant Anaesthetist, Royal Lancaster Infirmary said: “Whilst it is early days, the prospect of a monitor of anaesthetic depth that relies on measurements of the circulation and respiration is very attractive.”

  • doi:10.1111/anae.13208


Date of upload: 14th Mar 2017

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