Your Brain on Surgery

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

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The hid­den im­pact of anes­thetic on re­cov­ery

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 sys­tem­wise. 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 gen-

“It’s sober­ing to re­al­ize that no one quite un­der­stands how anes­the­sia works”

eral 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 pre­dis- pos­ing 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 an es th es ia-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 candi- dates 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.”

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