Doctors knock out sheep to discover anesthesia's dark side

SYDNEY (BLOOMBERG) – Beneath green surgical sheets and a tangle of tubes, a healthy young ewe is undergoing a heart-lung bypass procedure to help answer one of several urgent questions about a pillar of modern medicine: anesthesia.

Almost two centuries after anesthetics revolutionized surgery, a growing body of research is pointing to disturbing side effects that range from delirium to cancer-proliferating immune suppression.

Researchers knocked out the sheep last month at the University of Melbourne to try to understand why common open-heart procedures lead to acute kidney injury in up to a third of patients – part of a broader effort to study the impact of anesthesia on the immune system, brain and other major organs.

The findings are already undermining decades of soothing messages about the harmlessness of being put into a sleep-like state.

“Anesthetists are now trying to say actually it’s not that safe,” said Andrew Davidson, head of anesthesia research at the Murdoch Children’s Research Institute in Melbourne. “You don’t die on the table, but quite a lot of you don’t get home.”

Of the 200 million adults worldwide who undergo non-cardiac surgery annually, more than 1 million will die within 30 days. That risk jumps to 1 in 20 for patients 70 years and older.

Less than a mile from Davidson’s centre at the Royal Children’s Hospital in Melbourne, separate groups at the Florey Institute of Neuroscience and Mental Health and the Peter MacCallum Cancer Centre are working to understand whether inhaled volatile gases like isoflurane and sevoflurane – used by anesthetists to render some 80 per cent of patients unconscious – may be more harmful than intravenous agents, such as propofol and fentanyl.

With 313 million operations undertaken each year, the findings may have significant global economic and social implications, and could herald a paradigm shift in surgical care, researchers say.

The science is conflicting and incomplete. A study by Davidson and colleagues, published late Thursday in the Lancet medical journal, found an hour of general anesthesia in early infancy has no lasting impact on the developing human brain.

But some surgery may last longer, and Mayo Clinic doctors found an association between anesthesia and attention-deficit hyperactivity disorder in children.

The ADHD link is “scientifically plausible, but the evidence is not strong,” according to Davidson.

Sheep Probe

On the fourth floor of a University of Melbourne laboratory building, scientists at the Florey Institute are using fiber optic probes to measure blood flow and oxygen levels in different regions of the kidney of the 2-year-old Merino undergoing open-heart surgery.

The research, conducted by a team of clinicians and scientists under human surgical conditions, is designed to track kidney changes before, during and after the procedure, as well as identify risks attributable to two kinds of anesthetic agents, and find ways to protect the blood-filtering organ.

As many as 30 per cent of patients who undergo open-heart surgery develop an acute kidney injury that increases their risk of chronic kidney disease and death, according to Yugeesh Lankadeva, a researcher studying the interaction.

Lankadeva and colleagues showed in a paper published last month that volatile-gas anesthesia was associated with higher activity in a key nerve that corresponded with a potentially damaging reduction in blood flow to the kidneys of sheep during abdominal surgery. Intravenous anesthesia had less impact.

Lankadeva’s current study aims to understand the mechanism in the context of heart-lung bypass procedures – routinely used for cardiac grafts and valve replacements – when the kidney is susceptible to further injury due to a rush of blood after normal circulation resumes.

It’s possible that the nerve activation associated with anesthesia, especially the inhaled gas form, is also impairing the immune system, according to Clive May, head of the Florey Institute’s preclinical critical care unit, who developed the kidney probe technique.

“There is a well-known link between the nervous system and the immune system, and activation of the nervous system can inhibit the immune system,” May said.

That link is being explored across the road at the Peter MacCallum Cancer Centre. Researchers there will lead an international clinical trial this year involving 5,700 patients randomised to receive either type of anesthesia for lung or colorectal cancer surgery, and followed for five years to compare cancer recurrence and survival.

Informing Guidelines

Laboratory research and clinical observations indicate volatile gases may be harmful, said Bernhard Riedel, who is leading the study.

“But what we really need is a big prospective, randomised study to look at the body of evidence where we can change guidelines.”

Previous research suggests that inhaled anesthetics have a pro-inflammatory effect that may paralyse the immune system for about a week around the time of surgery, Riedel said. That could provide an opportunity for any cancer cells remaining in the body to gain a foothold at the same time as the gas anesthesia inadvertently encourages blood-vessel growth to support nascent tumors.

Propofol, on the other hand, may have an anti-inflammatory effect, causing less immune perturbation, he said.

When it comes to anesthetic’s effects on the brain, both anesthesia types appear to be implicated in damage to neurons, the organ’s basic working units – similar to what occurs from a concussion or a minor acute brain injury, according to Lis Evered, a University of Melbourne researcher.

Evered, who is also a neuroscientist at the city’s St Vincent’s Hospital, and colleagues showed last year increases in two biomarkers of neurological injury – neurofilament light and tau protein – in patients 60 years and older undergoing anesthesia on whom blood samples were taken before and sequentially up to 48 hours after surgery.

Compromising Cognition

Studies in elderly patients have also linked a longer duration of anesthesia to an increased risk of post-surgery delirium – a transient complication associated with poorer neurocognitive function longer term.

These raise questions about the risk-versus-benefit of some surgeries in older adults, Evered said.

“For 140 years, we were just concerned about safety,” she said. “In the last 30 years, we’ve actually become a bit more concerned about other sorts of impacts because people are living longer. Now, we want people to survive the procedure and have a good quality of life for the next 10 to 20 years.”

The findings of neurotoxicity are further challenging traditionally held beliefs that general anesthesia simply “turns the brain off” for a period after which it reverts to its pre-anesthesia state, said Davidson at the Murdoch Children’s Research Institute.

“Anesthesia is a very abnormal state for the brain to be in,” he said. “So it makes sense that your brain circuitry is actually not the same after the anesthetic as it was before.”

That probably doesn’t matter for young adult patients, Davidson said.

“But if you’re old or very young, then maybe it does begin to matter.”

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He Performed Surgery in Romania, but Is He a Doctor?

He looked like a handsome doctor straight out of a TV series.

On his Facebook page, Dr. Matthew Mode promoted cosmetic procedures, including surgery, performed at a clinic in a wealthy part of the Romanian capital, Bucharest. He posed in blue scrubs with a broad smile and a syringe of Botox.

But the authorities in Romania said this week that he was not authorized to practice medicine there, and questions have been raised about whether he is really a doctor.

Oh, and his name isn’t Matthew Mode.

Romanian health authorities began looking into Matteo Politi — the name he used before calling himself Matthew Mode — after news reports that he had operated on at least one woman without proper credentials. Almost a year after he began practicing medicine in Bucharest, prosecutors there have opened a criminal investigation into his actions.

On Wednesday morning, Romanian border guards found him trying to leave the country on a train bound for Budapest, removed him and handed him over to the police.

He did receive an identification code as a health care provider, in the name of Matteo Politi, from Bucharest’s public health authority in March last year. But on Tuesday the agency apologized for issuing the code and said in a statement that it was investigating how that had happened.

That code alone should not have been enough for Mr. Politi, who had emigrated from Italy, to practice medicine in Romania. He also needed authorizations from the Ministry of Health and the Romanian College of Physicians; both the ministry and the college said he did not have those credentials, and that they had begun investigations.

He had good reason for not promoting himself as Matteo Politi, according to Italian news organizations. Under that name, they reported, he had been convicted in 2011 of posing falsely as a doctor in Italy, and had received a suspended prison sentence.

The story of his Romanian exploits first appeared this week in the popular tabloid Libertatea. Soon after, he took down his Facebook page.

“I’m not fleeing, I just prefer not to say where I am,” Mr. Politi said Tuesday in a telephone interview with an evening talk show on Antena 1, a Romanian television network

“From the moment I was recognized, with a lawyer’s help, I can call myself a doctor,” he said. “My degrees were recognized and validated.”

But it is was not clear what degrees he actually holds.

On Facebook, Mr. Politi boasted regularly of his medical skill. Recent posts included a picture of him in a suit with the caption, written in both English and Romanian, “#DrMatthewMode, a doctor you can trust!” Another one said, “It’s important to always choose the best doctor! (meaning #DrMatthewMode).”

But in a video posted recently to Facebook, he seemed more like a playboy than a serious doctor, giving a “V” sign with his fingers and clutching a roll of Romanian bank notes.

“So Friday night, surgery, working, ready for party,” Mr. Politi said in the video, in heavily accented English, flanked by a giggling female co-worker. The caption said, “Friday afternoon pre-surgery and crazy mood.”

In another video, a woman who appeared to be a patient thanked Dr. Matthew Mode for her new lips.

Monza Hospital, a private clinic in Bucharest, confirmed that a man named Matteo Politi operated on one female patient in December. But the consultations leading up to the surgery took place in another medical institution, a statement on the clinic’s website said on Tuesday.

“Monza Group declares itself the injured party in this case and has begun legal action against Matteo Politi,” the statement said.

Mr. Politi’s story has drawn attention to possible loopholes in Romania’s struggling health system, in which private hospitals play a growing role alongside the state-run network. The country’s health minister, Sorina Pintea, recently announced that there would be more checks on the private system after cases of malpractice came to light last year, and she noted that medical impostors existed in other countries.

Last year, British medical authorities announced a review of the credentials of some 3,000 foreign physicians who began practicing in Britain before 2003, when checks were less stringent. The review was prompted by the case of Zholia Alemi, 56, a medical-school dropout, who worked at medical facilities around Britain before a news investigation found that she had been practicing under false pretenses.

In Italy, a number of dental technicians have passed themselves off as dentists, but the profession has taken steps to address the problem, said Filippo Anelli, president of Italy’s federation of medical guilds. Cases of fake doctors, he said, are “extremely rare.”

Elisabetta Povoledo contributed reporting from Rome.

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Justice Ginsburg Will Miss Supreme Court Arguments

Justice Ruth Bader Ginsburg, who underwent cancer surgery last month, will not be on the bench on Monday when the court returns from its holiday break, Kathleen Arberg, a Supreme Court spokeswoman, said.

Justice Ginsburg, who is working from home, would participate in the two cases to be argued Monday by reading briefs, other filings and the argument transcript, Ms. Arberg said.

Justice Ginsburg, who has undergone two other cancer surgeries, has never before missed an argument in her 25 years on the court.

Surgeons removed two nodules from Justice Ginsburg’s left lung on Dec. 21. The nodules were discovered during tests following a fall in November in which Justice Ginsburg fractured her ribs.

According to the justice’s thoracic surgeon, Dr. Valerie W. Rusch, the nodules removed during surgery were found to be malignant, Ms. Arberg said at the time.

After the surgery, “there was no evidence of any remaining disease,” she said, adding: “Scans performed before surgery indicated no evidence of disease elsewhere in the body.”

Justice Ginsburg, 85, is the senior member of the court’s four-member liberal wing. She has repeatedly vowed to stay on the court as long as her health holds and she stays mentally sharp.

President Trump has appointed two new members to the Supreme Court, Justices Neil M. Gorsuch and Brett M. Kavanaugh, moving it considerably to the right.

Should he name Justice Ginsburg’s replacement, Republican appointees would outnumber Democratic ones six to three.

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New clinical programme at National Heart Centre for patients with blood clots in lungs

SINGAPORE – For more than 30 years, Mr Ong Chee Fatt, 57, would keep fit by running 15 rounds around his flat every evening without fail, a distance of about 3km or 4km.

That routine came to an abrupt end in 2010, when he was 49.

“I felt like my fitness had suddenly dropped, even though there was no reason for it as I had been running consistently,” said Mr Ong, who was speaking during a media briefing on Thursday (Dec 6) at the National Health Centre Singapore (NHCS).

“Suddenly, I would feel breathless. It got so bad that I would have to stop after just half a round,” he added.

Although he did not know it at the time, Mr Ong had a condition known as chronic thromboembolic pulmonary hypertension (CTEPH), which affects about one in 10,000 people in Singapore.

In November 2016, he became one of the first few patients to undergo treatment for the condition as part of a programme that was being developed at NHCS.

The programme is now fully operational and accepting new patients.

Patients with the condition have high blood pressure in their lungs caused by clotting in the blood vessels.

Mr Ong, a senior lecturer who teaches civil engineering at Singapore Polytechnic, was recommended surgery called pulmonary endarterectomy.

Under this procedure, his body temperature was gradually lowered to 20 deg C to slow down his metabolism.

At this temperature, his heart stopped pumping and a machine took over his blood circulation.

The machine then completely drained his body of blood. Surgeons had 20 minutes to operate on his lungs to attempt to remove the clots.

Without cooling the body, irreversible brain damage would start to set in and other organs would begin to fail in just three minutes.

After the clot was removed, the blood was pumped back into Mr Ong’s body and he was returned to a normal temperature.

The procedure was repeated then to remove clots in the other side of his lungs, with the whole operation lasting about eight hours.

Following his recovery, Mr Ong went back to his old fitness routine.

“Before the surgery, I would even have problems walking up the slope to get to this clinic,” said Mr Ong, who is married with three children.

However, not all patients with his condition are suitable for the surgery.

Mrs Linda Ang, 40, similarly experienced breathlessness when climbing stairs.

She was recommended another surgery being offered under the programme known as balloon pulmonary angioplasty as she has a petite frame and a depression in her chest.

This surgery is more suitable for clots in smaller blood vessels, which surgeons might not be able to reach directly, said Associate Professor Lim Soo Teik, who is a senior consultant and deputy medical director at the department of cardiology in NCHS.

Under this procedure, a catheter was passed through a blood vessel in Mrs Ang’s leg to her lungs.

A tiny balloon device was then used to physically push the clot to the side of the blood vessels.

Mrs Ang, a former sales manager, underwent the procedure four times between May and November last year.

The two procedures being offered under the programme were not previously readily available in Singapore.

So far, a total of 22 people have undergone the procedures.

“Due to the non-specific nature of the symptoms and a lack of awareness of the condition, many cases go undiagnosed,” said Prof Lim.

“It is important that we raise awareness of this condition so that more can be diagnosed and treated early,” he added.

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