After a hip replacement, Nora Underwood found her body bounced back; her mind, however, took a little longer.

Even though I was only in my 50s, I knew I was going to have to have the surgery. I had severe arthritis in my left hip, probably the result of a left ankle break at the age of three that led to almost a dozen subsequent ankle breaks and, finally, a rebuild at the age of 17. (My dad used to joke, “It’s terrible having a daughter who’s always plastered.”) A gymnastics accident when I was 12 messed up my left sacroiliac joint at my pelvis and likely compounded the problem. I was always known for my walk –“I can tell it’s you from miles away,” people would say; I bounced, or so it appeared. But, really, my gait wasn’t high-spirited; it was messed up. A hip replacement was in the cards from the beginning.

I’m an anxious person by nature, though not as ruined by it as I was in my 20s, when the definition of a good day was not having to leave the house and only having a couple of panic attacks. The idea of surgery, especially such an invasive one, took me a while – and a lot of pain – to wrap my head around. By the time I had my replacement, in February this year, I was ready. I had read pretty much everything about what to expect; I had watched an animated version of the procedure on YouTube (several times); I had talked to everyone I knew who had had one; and I was in good physical shape – normal weight, strong and fit, or as fit as I could be with a crappy hip. Everyone told me it was going to be a cakewalk.

The day of the operation, I was given a spinal anesthetic and a sedative – enough, I had requested, so that I wouldn’t hear anything in the operating room. But at some point during the procedure, I did wake up. The anesthesiologist had explained that vital signs such as breathing and blood pressure are monitored constantly, and the dose of sedation is altered accordingly. I had very low blood pressure for a few days after the surgery, so perhaps the doctor had to ease up on the sedative. At any rate, I couldn’t feel any pain but I could hear sounds – a drill and other tools, people talking. It wasn’t upsetting at the time but perhaps it was a contributing factor to what happened later.

I was wide awake on the way to the recovery room, wide awake there, and quite euphoric for several hours after. My husband joked later that he had rarely seen me so happy. In less than 48 hours, however, everything changed. I woke up on the second day after surgery and all I could do was cry. I had never experienced anything like it – it was as if I were crying for all the sad things that had ever happened to anyone. I figured that once I was off the opioids – which I ditched on Day 3 – I’d be in the clear. But that kind of outburst would happen regularly over the next few weeks: suddenly I would be in tears and would not be able to stop for an hour or more. Worse, my panic attacks returned after many years of absence. For weeks after surgery, the attacks would come and go and, in between bouts, my resting level of anxiety had regressed 25 years. Even now as I write this, four months after surgery, I am not yet back to the person I was before, nervous system-wise. I’m jumpier, for sure, but also quick to tears, and my normally positive outlook (sometimes forced but mostly natural) is often elusive.

For years, doctors have anecdotally noted cognitive and mood-related changes in some of their patients after surgery, particularly after certain types of surgeries – heart, bariatric, vascular, neurological, hip and knee, among others. Cognitive problems run the gamut from disorientation and memory issues to delirium and even dementia, particularly in older patients. Many of these issues resolve themselves in days or sometimes weeks or months. “We’ve always heard stories about people not feeling quite well after surgery, and there’s literature to support that,” explains Dr. Beverley Orser, director of research at Sunnybrook Health Sciences Centre’s department of anesthesia and a professor of anesthesia and physiology at the University of Toronto. “One in three will show deficits at the time of discharge; one in 10 will still be showing them at three months.”

But Google a bit, and there’s much evidence in the general population that some post-surgery changes can last much longer. Indeed, in extreme cases, patients with something called post-operative cognitive dysfunction (POCD) can suffer from memory and concentration problems for the rest of their lives, and a 2008 study noted that patients with POCD three months after discharge were almost twice as likely to die within a year after surgery than those who had no cognitive issues. In a 2001 study published in the New England Journal of Medicine, researchers focused on cognitive decline in patients – all of whom were older than 50 – who had undergone cardiac surgery and then followed them for five years. Of the 172 patients studied over those years, researchers documented cognitive decline in 53 per cent at discharge, 36 per cent at six weeks and 24 per cent at six months. But the number rose to 42 per cent at the five-year checkup, indicating that not only had some patients not improved, others had had a recurrence of cognitive problems. There is less documented information about mood changes but, as Orser notes, it is equally important for doctors to understand what happens to people’s sense of well-being after surgery.

You hear people say that someone they knew was never the same after surgery. My friend Jared’s parents were both affected in different ways by surgery. His father was 73 when he had a quadruple bypass. Like me, he came out of the recovery room “cheerful and joking with the nurses,” Jared recalls. “Two or three days later, he just got sadder and darker and sadder and darker to the point where he couldn’t do anything except stare at the ceiling.”

Fortunately, the changes lasted only 10 days or so but, Jared says, “He had no will to live after surgery.”

The effects his mother experienced after a hip replacement at 82, however, lasted without abating until her death three years later. “We got her home, and she went on about how the nurses were hanging around her all morning waiting for a tip,” Jared recalls, who adds that his mother showed no evidence of cognitive problems before the surgery. “She threw her pills under the bed; she’d lie to me and when I’d challenge her, she’d cry and talk to me in a little-girl voice. She had the mind of a child afterwards.”

Considering that post-operative brain and mood problems tend to be more prevalent in older patients and considering that the population as a whole is aging, getting a grip on post-operative disorders is only going to become more pressing. To that end, Sunnybrook recently established a Centre for Perioperative Brain Health – the first of its kind in the world – the goal of which is to understand the risks and severity of cognitive and mood changes in the post-operative period.

Researchers there and elsewhere already have several theories about what might be the culprits in post-op meltdown. One is anesthesia’s affect on the brain. It’s sobering to realize that no one quite understands how anesthesia works. Orser, one of the investigators at Sunnybrook’s new centre, calls it the million-dollar question. “We’re developing a better understanding of how anesthetics depress brain function,” she says, “but it’s not completely understood.” Generally, the drugs bind to sensors or receptors in the brain, preventing the nerves from carrying pain signals to the brain and preventing memories of the surgery. While it may be comforting to equate anesthesia with sleep, the drugs actually induce a coma in the patient, which is why an anesthesiologist monitors breathing and vital signs throughout an operation.

Dr. Sinziana Avramescu, an anesthesiologist and a member of the Sunnybrook research team, acknowledges that while the drugs that are used to blunt memory may be the culprit in post-operative troubles, “you want not to remember.” The expectation may have been that once the drugs are out the system, memory will return to its previous state. “But now we’re seeing that this doesn’t quite happen,” she adds. “We think that the link between the two is increased inflammation produced by the surgery itself or the anesthetic may increase inflammation in the brain. So if you have another inflammatory disease, like arthritis, it will all contribute to a higher risk of memory problems after surgery.”

In addition, she explains, there appears to be a connection between increased brain inflammation and people who develop or have a relapse of depression and/or anxiety. But the researchers are still trying to grasp how inflammation leads to these problems. Some anesthetic drugs increase the number of memory-blocking receptors, and while the drugs have worn off after a day, the effects of the anesthetic can last a longer time.

Dr. Stephen Choi, an anesthesiologist and director of clinical research at the centre, likens what can happen post-operatively to post-traumatic stress disorder: “When did they have their major traumatic event? While they were in Iraq,” he says. “However, when you’re back home, rationally there’s very little to fear, but there will be noises or certain visions that trigger the memories. Why is that? The anesthetics block the receptors; once they’re gone, there’s no reason for them to be overly active, but we think they possibly are. Or it must just be that there are more of them and, because of that, people are more sensitive to them.” In a recent article in Science online, Harvard Medical School anesthesiologist Gregory Crosby, who has written about surgery and the brain, is quoted as saying: “If you see how [anesthetized] people awaken, it’s absolutely not normal,” referring to their “disordered central nervous system.” He continues: “The only thing worse than general anesthetic is surgery … There’s nothing bigger that will happen to most people.”

Other theories include the effects of surgery itself and the necessary damage that is caused to get the problem solved. Cutting into tissue, as Dr. Nathan Herrmann, head of geriatric psychiatry at Sunnybrook, explains, releases all kinds of inflammatory proteins and immunological cascades that doctors know are associated with depressive-like symptoms. Another theory is symptoms may be precipitated by so-called “sickness behaviour” – adaptive changes, such as lethargy, anxiety, loss of appetite, concentration problems and so on, that occur in the body in response to illness. “The belief is that this is part of the healing process,” Herrmann explains, “so perhaps this is displayed as full-blown depression and particularly in cases of people who are vulnerable to depression.”

Then there’s the pain associated with surgery, the immobilization and loss of independence in some cases, the side effect of painkillers and other drugs used before, during and after surgery and so on. There’s the age of the patient, extent and duration of the surgery and predisposing problems. “We see it all the time – two patients of the same age, having the same surgical procedure: one can have post-operative delirium and memory impairment, and the other will be completely back to baseline,” explains Avramescu. “And this is what we want to understand: how do anesthetics and surgeries affect the brain? Who is at risk of having cognitive problems? How can we prevent it – and if we are not able to prevent it, how can we treat it?”

Now that anesthesia-related deaths have been reduced from one in 1,000 in 1940 to one in 100,000 in the early 2000s, the focus is shifting from simply keeping people alive during surgery to figuring out the mechanism by which anesthesia works and what long-term effects it might have and on who.

“Anesthesia has never been safer,” says Avramescu, “but we are now refining our skills and we need to move beyond the ‘ether era.’ ” And while the cause or causes of post-operative cognitive and mood problems – and the understanding of who is at risk – are far from clear, there is comfort in the fact that an increasing number of medical experts are taking the issue seriously.

For their part, surgery candidates are wise to minimize any and all risks on their end, Orser says, by understanding all the potential side effects of surgery and by practising good brain health – getting proper sleep, exercise, avoiding substances like alcohol and staying on top of chronic problems such as diabetes and hypertension before surgery. The vast majority of surgeries are not elective, despite being labelled as such – most are necessary, though not all are immediately necessary. “If you forgo surgery, cognitive changes are probably the least of your worries,” says Choi. Truly elective surgery, he adds, “is something that is completely unnecessary – your physical function or life are not in jeopardy. It is these types of procedures that people should really think twice about.”

Most of the time, however, the benefits far outweigh the risks. And by and large, people don’t enter an operating room lightly. “Most people are still more concerned about being alive after surgery than they are about being the same or better after surgery,” says Avramescu. “If surgery is indicated and will improve their well-being, they should absolutely have it.”

A version of this article appeared in the December 2017/January 2018 issue with the headline, “Your Brain on Surgery,” p. 62-66.