Executive Summary
A common claim among patients and families holds that repeated major surgeries under anesthesia, such as successive knee or hip replacements, carry serious mental consequences that are well known, yet that these procedures are often scheduled close together. The claim also holds that nurses and pharmacists may understand these risks better than surgeons do. The research literature supports part of this claim, complicates part of it, and does not yet answer the rest.
Three points stand out. First, short-term cognitive disturbance after major surgery in older adults is common, well documented, and clinically important. Second, the evidence that anesthesia itself, as opposed to surgery, inflammation, and the drugs given around the operation, causes lasting cognitive harm is mixed. Studies of cumulative exposure reach conflicting conclusions. Third, the clearest weaknesses lie in how knowledge moves through the system: who screens patients, who notices symptoms, who reviews medications, and who follows the patient after discharge.
1. Terminology
Older literature used “postoperative cognitive dysfunction” (POCD) loosely. In 2018 an international working group proposed a shared vocabulary. It recommended “perioperative neurocognitive disorders” as an umbrella term covering impairment found before surgery, acute postoperative delirium, cognitive decline found up to 30 days after the procedure (delayed neurocognitive recovery), and decline up to 12 months (postoperative neurocognitive disorder). The terms were tied to DSM-5 criteria. Critics noted at the time that the recommendations might be useful but were not yet complete, and that some terms were used imprecisely. This matters because studies using different definitions report very different rates. Comparison across the literature is therefore difficult.
Two conditions need to be kept apart:
- Postoperative delirium: an acute, fluctuating disturbance of attention and awareness, usually in the first days after surgery. It can be hyperactive (agitated), hypoactive (quiet and withdrawn), or mixed.
- Delayed neurocognitive recovery / postoperative neurocognitive disorder: subtler declines in memory, attention, or executive function, detected by testing over weeks to months.
2. What Is Known
2.1 Short-term cognitive changes are common in older surgical patients
The foundational study is ISPOCD1, published in The Lancet in 1998. It tested 1,218 patients aged 60 or older before major non-cardiac surgery and again at one week and three months afterward. Cognitive dysfunction appeared in about 26% at one week and about 10% at three months, compared with roughly 3% in matched controls. One finding bears directly on repeated surgery: longer anesthesia, less education, a second operation, postoperative infections, and respiratory complications were risk factors for early dysfunction, but only age predicted dysfunction at three months.
Later summaries put the incidence of perioperative neurocognitive disorders in older non-cardiac surgical patients at approximately 30% at one week, 10% at three months, and 1% at one year. Most patients recover. The ISPOCD group found no difference between surgical patients and controls at one to two years, and most patients with dysfunction at one week had recovered after several months.
Recovery is not universal, and the minority who do not recover face real consequences. A Danish follow-up of ISPOCD patients found that cognitive dysfunction at three months, though not at one week, was associated with increased mortality, and that postoperative dysfunction was linked to leaving the workforce early and depending on social payments.
2.2 Delirium is a recognized complication of joint replacement
For joint replacement specifically, researchers describe postoperative delirium as a serious and common complication in older adults, associated with higher risk of other postoperative complications, mortality, and longer hospital stays. Reported rates vary widely. A 2025 meta-analysis attributes this to differences in study populations, surgical procedures, diagnostic criteria for delirium, and perioperative management protocols.
The strongest predictor is the patient’s condition before surgery. Baseline cognitive deficit was the main risk factor for cognitive disorders after hip arthroplasty, and postoperative delirium predicted early postoperative cognitive dysfunction. The ASA Brain Health Initiative’s clinical summary likewise identifies pre-existing cognitive impairment as a significant risk factor for perioperative neurocognitive disorders.
2.3 Anesthesia type matters less than once believed
A long-standing assumption held that regional (spinal) anesthesia protects the brain better than general anesthesia. Two large randomized trials in hip fracture patients tested this.
The REGAIN trial enrolled 1,600 patients across 46 hospitals in the United States and Canada. Delirium occurred in 20.5% of the spinal group versus 19.7% of the general group. A secondary analysis of patients who already had cognitive impairment found that anesthesia type was not associated with differences in delirium or functional recovery, whether or not preoperative impairment was present.
The RAGA trial in China went further by avoiding all sedation in the regional arm. Delirium occurred in 6.2% of the regional group and 5.1% of the general group, with similar severity and type. An editorial on the trial concluded that its results support the view that avoiding sedative-hypnotic medications does not prevent postoperative delirium, while raising the possibility that excessively deep anesthesia, rather than general anesthesia as such, may be harmful.
These trials involved emergency hip fracture repair, not elective joint replacement. Still, they shift attention away from the anesthetic agent alone and toward the whole surgical event: tissue injury, inflammation, pain, sleep disruption, hospitalization, and the many other drugs a patient receives.
2.4 Medications around surgery are a known, modifiable risk
The best-established precipitating factors are drugs given before, during, and after the operation. The American Geriatrics Society Beers Criteria list medications to avoid in older adults. A University of California, San Francisco quality improvement study notes that drugs commonly used around surgery that contribute to delirium in older patients include anticholinergic drugs such as diphenhydramine and scopolamine, benzodiazepines, and meperidine. A case report illustrates how easily these accumulate: a geriatric patient undergoing an uncomplicated procedure received multiple potentially inappropriate medications, including midazolam, metoclopramide, glycopyrrolate, and dexamethasone.
Interventions targeting these drugs work. The UCSF program found that a perioperative delirium prevention intervention was associated with reduced administration of Beers-listed medications to older adults. At a large university hospital, an educational video followed by an electronic health record alert advising over 300 anesthesia practitioners to reduce or omit Beers medications in patients 70 and older produced a significant reduction in their use.
2.5 Cumulative exposure: the evidence conflicts
The central question raised by the original claim, whether multiple surgeries compound harm over time, has no settled answer. The studies split.
Studies finding no association:
- A Mayo Clinic population study found no significant association between cumulative surgical anesthesia exposure after age 40 and mild cognitive impairment, whether measured by number of exposures or total cumulative duration.
- A prospective Group Health study concluded that anesthesia exposure was not associated with increased risk of dementia or Alzheimer’s disease in older adults. However, it also found that high-risk surgery with general anesthesia, compared directly with other surgery under general anesthesia, carried a higher hazard for both dementia and Alzheimer’s, and called for further study.
Studies finding an association:
- A nationwide cohort of about 219,000 people published in the Journal of Alzheimer’s Disease in 2018 reported that dementia risk was increased after general anesthesia, and that the number of anesthetic agents, the number of exposures, cumulative exposure time, and the organ category of surgery were all associated with dementia risk.
- The 12-year Maastricht Aging Study, reported in 2025, found that greater time under general anesthesia at baseline correlated with significant decline in three of four cognitive domains, though to a lesser extent than aging and comorbidities.
The disagreement likely reflects a basic problem with observational data. People who need many surgeries are, on average, sicker, older, and more frail than those who need few. Separating the effect of anesthesia from the effect of the underlying illness that required surgery is very difficult without randomized trials, and randomizing people to repeated surgery is not possible.
3. Who Holds the Knowledge
The original claim suggests that knowledge is unevenly distributed among professions. The evidence partly bears this out, but the picture is more complicated than “surgeons know less, nurses and pharmacists know more.”
Anesthesiologists. It is worth noting that surgeons do not administer anesthesia; anesthesiologists and nurse anesthetists do. The anesthesia profession has led organized attention to this problem. The American Society of Anesthesiologists created its Perioperative Brain Health Initiative in partnership with AARP and other stakeholders, including the American College of Surgeons. A working group under that initiative organized its best-practice recommendations around preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up.
Surgeons. Orthopedic decision-making about staging tends to focus on mechanical and medical complications. A 2025 meta-analysis concluded that simultaneous bilateral knee replacement lowers reoperation and cost at the expense of higher complications and mortality. Earlier reviews found that simultaneous procedures carry higher rates of mortality, pulmonary embolism, and transfusion, but lower rates of deep infection and revision. Cognitive outcomes rarely appear among the measured endpoints in this literature. Some cohorts exclude cognitively impaired patients outright: one study states that individuals with cognitive impairment, psychological illness, or a history of addiction or balance disorders were not included. That exclusion removes from the evidence base precisely the patients most at risk.
Nurses. Nurses hold a structural advantage: they have a far higher rate of patient interaction than any other healthcare professional. Yet research consistently shows that this proximity does not automatically produce recognition. In a landmark study by Inouye and colleagues, nurses identified delirium in only 31% of affected patients compared with researchers, and hypoactive delirium raised the odds of under-recognition about sevenfold. A Cleveland Clinic study found that in one cohort, an advanced practice nurse found 24 patients positive for delirium, while ward nurses identified only four. Nurses report barriers of their own: inadequate time with patients, and the importance of nurse-physician communication for detection and treatment. Training improves detection, but the claim that nurses already know better than physicians is not well supported as a general rule. Individual experienced nurses may well have sharp clinical judgment; the profession as a whole has documented blind spots.
Pharmacists. Pharmacists bring specific expertise in drug interactions, anticholinergic burden, and the Beers Criteria. A Korean study of surgical oncology patients concluded that a pharmacist’s comprehensive review of preoperative medications is critical for outcomes such as delirium in older patients. A Veterans Affairs evaluation found that documented risk-benefit assessment of anticholinergic use in veterans with dementia occurred only about 13% of the time, which illustrates how often this knowledge goes unapplied when no one is assigned to apply it. However, evidence for pharmacist-led prevention specifically in surgery is still thin. A Japanese cardiovascular study noted that pharmacist-led interventions have shown limited evidence for reducing postoperative delirium in cardiovascular surgery.
Geriatricians. Geriatric medicine has produced much of the prevention evidence. A review in Current Opinion in Critical Care notes that perioperative geriatric consultation, early surgery, effective pain management, and staff education have reduced the incidence and severity of delirium in hip-fracture patients. Geriatric consultation is not routine for elective joint replacement in most settings.
Families. Families often notice changes that no clinician sees, because the subtler cognitive declines appear after discharge. An ASA representative described patients reporting that they can no longer do the crossword or find their car. These observations rarely reach the surgical team.
4. Gaps in Knowledge
- Attribution. Researchers still cannot cleanly separate the effects of the anesthetic, the surgery, inflammation, pain, opioids, sleep loss, and hospitalization. The RAGA and REGAIN results suggest the anesthetic agent alone is not the main driver of delirium, but they leave the role of anesthetic depth and accompanying drugs open.
- Cumulative and repeated exposure. Large observational studies disagree on whether multiple surgeries raise long-term dementia risk. No study has resolved confounding by underlying illness.
- Optimal spacing between staged procedures. The literature comparing simultaneous and staged bilateral joint replacement measures mortality, clotting, transfusion, infection, and cost. It says little about cognition. There is no evidence-based minimum interval for cognitive recovery between procedures. A randomized trial comparing staged and simultaneous bilateral knee arthroplasty (NCT03564730) has an estimated completion in December 2026, but its registered description does not indicate a cognitive endpoint.
- Long-term outcomes in the most vulnerable. Many joint replacement studies exclude patients with existing cognitive impairment, who face the highest risk.
- Measurement. Definitions, tests, and timing vary so much that incidence figures range widely. The 2018 nomenclature was meant to address this, but adoption is incomplete.
- Interventions. The Brain Health Initiative summary states that multicentre randomized trials and observational studies are still needed to determine whether current best-practice recommendations reduce perioperative neurocognitive disorders.
5. Gaps in Application
Even where knowledge exists, it often does not reach practice.
- No preoperative cognitive baseline. Without a baseline test, postoperative decline cannot be measured. A German review observed that detecting perioperative neurocognitive disorders depends on extended neuropsychological testing that is often not feasible because of economically driven time constraints during preoperative assessment.
- Informed consent rarely addresses cognition. ISPOCD’s authors stated in 1998 that their findings had implications for the information given to patients before surgery. Nearly three decades later, cognitive risk is still not a standard part of consent conversations for elective joint replacement.
- Detection depends on staff who are not trained to find the quiet form. Hypoactive delirium, the form most often missed, looks like a calm, tired patient rather than a confused one.
- Short hospital stays move the problem home. Joint replacement has shifted toward same-day or one-night stays. Delirium and delayed recovery that emerge afterward fall to family members who may not recognize them and have no clear clinician to call.
- Medication review is not routinely assigned to anyone. Pharmacist review of anticholinergic and sedative burden is effective where it happens, but most surgical pathways do not require it.
- No one owns postoperative cognition. The surgeon follows the joint, the primary care physician follows chronic disease, and the anesthesiologist’s responsibility ends at recovery. Cognitive follow-up falls between these roles.
- Scheduling decisions draw on incomplete outcome data. When staging intervals are chosen, the evidence that informs them weighs blood loss, clotting, and cost. The cognitive dimension is largely absent, not necessarily from neglect but because the data do not exist.
6. Assessment of the Original Claim
- “There are serious mental consequences with multiple replacement surgeries and anesthesia.” Partly supported. Cognitive disturbance after major surgery in older adults is common and sometimes lasting, and a prior operation is a documented risk factor for early dysfunction. Whether repeated surgeries cause lasting cumulative harm remains unresolved, and the anesthetic itself may matter less than the surgical event and surrounding medications.
- “This is well known.” Well known among anesthesiologists and geriatric specialists; much less consistently known among patients, families, and some surgical teams, and not consistently reflected in consent or scheduling.
- “Surgeons schedule surgeries close in time.” Close staging, including intervals of a week, is a recognized practice. The evidence base guiding it largely omits cognitive outcomes.
- “Nurses and pharmacists may be more aware.” Pharmacists have specialized knowledge of the drugs most strongly linked to delirium and are underused. Nurses have the most patient contact and are crucial observers, but studies show they frequently miss delirium, especially the quiet form, unless trained and given standardized tools. Experience and judgment vary by individual more than by profession.
7. Recommendations
For health systems:
- Screen cognition before elective surgery in patients over 65, using brief validated tools, so that a baseline exists.
- Build pharmacist medication review, focused on Beers-listed drugs and anticholinergic burden, into the standard joint replacement pathway.
- Use electronic health record alerts for high-risk medications in older patients.
- Train nursing staff in standardized delirium screening with emphasis on the hypoactive form.
- Assign clear responsibility for cognitive follow-up after discharge.
For researchers:
- Include cognitive endpoints in trials comparing staged and simultaneous joint replacement and different staging intervals.
- Stop excluding cognitively impaired patients from studies whose findings will be applied to them.
- Adopt the 2018 nomenclature consistently to allow comparison across studies.
For patients and families:
- Ask the surgical and anesthesia teams about cognitive risk, especially when bilateral or closely spaced procedures are proposed.
- Request a medication review before surgery, including over-the-counter sleep aids and allergy medications.
- Know what a baseline looks like so that changes after surgery can be recognized.
- Report new confusion, unusual sleepiness, or withdrawal promptly, even after discharge.
Conclusion
The problem described in the original claim is real, but its shape differs from the popular version. The anesthetic agent is probably not the sole or main villain. The larger issue is that the surgical event, the drugs given around it, and the patient’s prior condition combine to produce cognitive harm that is common, usually temporary, occasionally lasting, and frequently unnoticed. Knowledge of these risks is spread across professions that do not consistently share it, and the decisions about scheduling repeated surgeries rest on evidence that measures nearly everything except the mind of the patient.
Sources:
- ISPOCD1 study, Lancet 1998 (PubMed)
- ISPOCD1 study abstract (Maastricht University)
- ISPOCD long-term follow-up (BMJ / PMC)
- Long-term consequences of POCD, Anesthesiology 2009
- Recommendations for nomenclature of cognitive change, 2018 (PMC)
- ASA news release on new nomenclature
- Medical Design and Outsourcing on nomenclature critiques
- ASA Brain Health Initiative clinical summary, BJA
- Best Practices for Postoperative Brain Health (PubMed)
- Connal, Perioperative neurocognitive disorders, Br J Hosp Med 2023
- Delirium after TJA in South East Asians, BMJ Open
- Ni et al., POD after TJA meta-analysis, Front Med 2025
- Politov et al., anesthesia and cognitive disorders after arthroplasty
- ACC summary of REGAIN
- REGAIN secondary analysis, Network for Investigation of Delirium
- ASRA literature review on REGAIN and RAGA
- JAMA editorial on RAGA (PMC)
- Simultaneous vs staged bilateral TKA meta-analysis, 2025
- Orthobullets systematic review summary
- simBTKA vs stgBTKA by age (PMC)
- UCSF perioperative delirium prevention initiative (PMC)
- Case report on avoiding inappropriate medications (PMC)
- Penn Beers Criteria quality improvement project
- Pharmacist-driven deprescribing in veterans with dementia
- Pharmacist-led intervention in cardiovascular surgery, PLOS One
- Preoperative medication use and POD in surgical oncology (PMC)
- Monk and Price, Postoperative cognitive disorders (PMC)
- Mayo Clinic cumulative anesthesia and MCI study (PMC)
- Aiello Bowles et al., anesthesia and dementia, JPCRR
- General anesthesia and dementia nationwide cohort, J Alzheimers Dis
- NYSORA summary of Maastricht Aging Study
- Inouye et al., Nurses’ recognition of delirium
- Cleveland Clinic on missed delirium in cardiac patients
- Barriers to surgical nurse detection of delirium
- Nurse delirium education study
- Implementation of pNCD screening, Thieme
- Staged vs simultaneous bilateral knee RCT, NCT03564730
This is a sensitive health topic, and nothing here substitutes for a conversation between a patient and the clinicians managing a specific surgery.
