The science of Perioperative Health.

Key finding

Nearly half of adults having elective colon resection had low plasma vitamin C after surgery: 13.7% met criteria for deficiency and a further 33.3% had hypovitaminosis C (47% overall). The authors note that micronutrient assessment is seldom part of ERAS pathways.

Clinical significance

Colorectal surgery quality programs focus on sterility, glycemia and fluids. This study identifies micronutrient status as a common and largely unmeasured variable in the same population.

Key finding

Across seven observational studies of 3662 patients having esophageal or gastric cancer surgery, malnutrition defined by GLIM criteria was associated with more postoperative complications (pooled HR 2.58, 95% CI 1.45–4.59) and shorter overall and disease-free survival.

Clinical significance

GLIM gives malnutrition a shared diagnostic definition. This pooled analysis shows that a standardized nutritional diagnosis before surgery carries prognostic information for complications and survival.

Key finding

Anesthesiologists' subjective estimate of functional capacity identified only 19.2% of patients unable to reach four METs on cardiopulmonary exercise testing. Among CPET, NT-proBNP, the Duke Activity Status Index (DASI) and subjective assessment, only DASI scores were associated with 30-day death or myocardial infarction (adjusted OR 0.96 per point). The authors concluded subjective assessment should not be used for preoperative risk evaluation.

Clinical significance

This multicenter study helped shift how functional capacity is assessed before surgery, moving assessment from clinical impression toward short structured questionnaires such as DASI.

Key finding

Across 12 studies, preexisting sleep disturbance was associated with postoperative delirium (pooled OR 5.24, 95% CI 3.61–7.60), with a risk ratio of 2.90 in the six prospective studies. Obstructive sleep apnea and unspecified sleep disorders showed similar associations.

Clinical significance

Sleep is a preoperative state that is measurable and potentially modifiable, and here it tracks with one of the most consequential perioperative neurocognitive disorders. The authors identify trials targeting sleep as the open question.

Key finding

In patients having cardiac surgery with cardiopulmonary bypass, plasma vitamin C fell significantly during bypass and did not recover through discharge on postoperative day 6. A marker of lipid peroxidation (malondialdehyde) rose sharply after unclamping, and the ascorbyl radical to ascorbate ratio stayed elevated throughout.

Clinical significance

Surgery can deplete a key antioxidant micronutrient and keep it low through early convalescence. Micronutrient status is dynamic across the surgical window, not fixed at the preoperative baseline.

Key finding

In 227,425 patients having major non-cardiac surgery, 30% had preoperative anemia. Anemia, even mild, was independently associated with higher 30-day mortality (adjusted OR 1.42, 95% CI 1.31–1.54) and composite morbidity (adjusted OR 1.35, 95% CI 1.30–1.40).

Clinical significance

Preoperative anemia is common, detectable weeks before surgery and associated with worse outcomes at mild levels. This study helped establish anemia screening as a preoperative optimization target and informs patient blood management.

Key finding

In 594 adults aged 65 and older having elective surgery, frailty was independently associated with postoperative complications (frail: OR 2.54, 95% CI 1.12–5.77), longer stay, and discharge to a skilled or assisted-living facility (frail: OR 20.48). Adding frailty improved the predictive power of the ASA, Lee and Eagle risk indices.

Clinical significance

Frailty captures physiologic reserve that diagnosis-based risk scores miss. This study helped establish standardized frailty assessment as part of preoperative evaluation in older adults.

Key finding

Elective hip replacement reduced insulin-stimulated glucose disposal immediately after surgery. Muscle biopsies showed reduced nonoxidative glucose disposal and glycogen synthase activity, with impaired GLUT-4 translocation in half of patients, locating the insulin resistance in skeletal muscle.

Clinical significance

Surgical insulin resistance is a direct physiologic consequence of the operation, not only of illness or fasting. This mechanistic work underpins the metabolic rationale for modern perioperative feeding and glycemic practice.

Key finding

In 847 adults aged 60 and older with frailty, offering coach-supported, home-based prehabilitation (exercise plus personalized nutrition recommendations) did not improve 30-day disability or reduce in-hospital complications compared with publicly available guidance. Participants completed a median of 4 weeks; competing priorities and motivation were the main barriers to adherence.

Clinical significance

This large pragmatic trial shows that offering prehabilitation is not the same as delivering it. Adherence and program design now sit at the center of prehabilitation research for older surgical patients.

Key finding

The 2025 ESPEN guideline sets out 44 recommendations for nutrition in elective and non-elective surgery. Its core principles: integrate nutrition into overall management, avoid long preoperative fasting, restart oral feeding as early as possible, begin nutritional therapy as soon as nutritional risk is apparent, maintain metabolic control, and mobilize early. New recommendations cover frailty assessment, sarcopenia diagnosis and prehabilitation.

Clinical significance

This is the current European standard of care for surgical nutrition. It treats nutrition as part of perioperative management rather than an adjunct, and it extends that responsibility to preparation before surgery.

Key finding

Across three randomized trials (250 patients), a four-week trimodal prehabilitation program (exercise, nutrition, anxiety reduction) before colorectal cancer surgery improved preoperative 6-minute walk distance by 24.9 meters (95% CI 11.2–38.6; moderate certainty). Effects on complications, emergency department visits and readmissions were small or trivial.

Clinical significance

Multimodal prehabilitation improves functional capacity before surgery, on moderate-certainty evidence. Whether that gain changes clinical outcomes is the central unanswered question, and this review frames the trials needed to answer it.

Key finding

Across nine studies (914 patients) of colorectal surgery, nutritional prehabilitation for at least seven days, alone or combined with exercise, reduced hospital stay by 2.2 days (95% CI 0.9–3.5) compared with no prehabilitation. Individual trials showed faster return to presurgical walking capacity with multimodal programs.

Clinical significance

Nutrition delivered before surgery, not only after it, was associated with a meaningful difference in hospital stay. This review helped move preoperative nutrition from a supportive measure to a component of preparation.

Key finding

An international ASER and Perioperative Quality Initiative consensus made a strong recommendation for routine preoperative nutrition screening to identify patients who need nutritional optimization before surgery. It recommends restarting nutrition immediately after surgery, prioritizing protein over total calories, and supporting nutrition after discharge with oral supplements.

Clinical significance

Malnutrition is a strong independent predictor of poor outcomes, yet U.S. implementation of perioperative nutrition guidance has been limited. This statement translates the evidence into a screening-first workflow that spans the whole surgical journey, including after discharge.

Key finding

Intensive preoperative smoking-cessation programs, beginning four to eight weeks before surgery with weekly counseling and nicotine replacement, increased abstinence at surgery (RR 10.76) and reduced postoperative complications (RR 0.42, 95% CI 0.27–0.65) and wound complications (RR 0.31). Brief interventions increased short-term quitting modestly (RR 1.30) but did not reduce complications.

Clinical significance

Smoking is one of the clearest modifiable perioperative risks, and the scheduling of surgery is a natural moment for behavior change. The finding that intensity and lead time determine benefit makes preoperative timing a design variable, not an afterthought.

Key finding

Across 27 randomized trials (1976 patients), a preoperative carbohydrate drink (at least 45 g within four hours of surgery) improved postoperative insulin sensitivity (high-quality evidence) and was associated with a modest reduction in hospital stay of 0.30 days compared with placebo or fasting. Complication rates did not change (RR 0.98), and no aspiration pneumonitis was reported.

Clinical significance

Replacing overnight fasting with a carbohydrate drink improves postoperative insulin sensitivity, and no aspiration pneumonitis was reported across the included trials. This evidence underlies the move away from 'nothing by mouth after midnight' in ERAS pathways.

Key finding

In patients having colorectal cancer resection, a four-week multimodal program started before surgery increased walking capacity before the operation in 53% of patients vs 15% when started after surgery. At eight weeks, 84% vs 62% had recovered to baseline exercise capacity (6-minute walk difference 45.4 m, 95% CI 13.9–77.0). Complications and length of stay were similar.

Clinical significance

This trial showed that the weeks before surgery are a usable window for changing a patient's recovery trajectory. It shaped the design of prehabilitation research that followed.

Key finding

Across 18 trials (1463 patients) of hip or knee replacement, generic preoperative education did not clearly improve postoperative anxiety, pain, function or adverse events over usual care. The authors suggest education stratified to need may help selected patients, such as those with anxiety, depression or unrealistic expectations.

Clinical significance

Information alone is not preparation. This review shows why one-size education rarely moves outcomes and points toward education tailored to the patient's physical, psychological and social needs.

Key finding

The American Society of Anesthesiologists' 2023 modular update to its preoperative fasting guideline addresses three questions not covered previously: carbohydrate-containing clear liquids with or without protein, chewing gum, and fasting duration in children.

Clinical significance

Preoperative fasting rules are among the most consequential routine instructions a surgical patient receives. This update brings carbohydrate-containing drinks formally into the U.S. anesthesiology guideline framework.

Key finding

The fourth ERAS Society guideline for elective colorectal surgery gives a graded recommendation for every element of the enhanced recovery protocol, from preadmission through discharge. Each recommendation is rated by GRADE, drawing on meta-analyses, randomized trials and large prospective cohorts.

Clinical significance

This is the reference protocol for colorectal ERAS and a template that other specialties have adapted. It defines perioperative care as a sequence of evidence-graded elements spanning before, during and after surgery.

Key finding

In 3000 patients at increased risk having major abdominal surgery, a restrictive intravenous-fluid regimen (median 3.7 L vs 6.1 L over the first 24 hours) did not improve one-year disability-free survival (81.9% vs 82.3%) and was associated with more acute kidney injury (8.6% vs 5.0%).

Clinical significance

RELIEF reversed a widely adopted ERAS assumption that less intravenous fluid is better. It supports a moderately liberal, balanced approach and shows why individual pathway elements need their own trials.

Key finding

Enhanced Recovery After Surgery is a multimodal, multidisciplinary care process that replaces overnight fasting with carbohydrate drinks two hours before surgery, favors minimally invasive approaches and balanced fluids, and promotes early feeding and mobilization. The authors report that ERAS protocols have shortened hospital stay by 30% to 50%, with similar reductions in complications.

Clinical significance

ERAS showed that coordinated, protocolized care across the whole surgical episode changes outcomes. Its emphasis on auditing compliance made measurement part of the intervention.

Key finding

Across 25 placebo-controlled randomized trials, perioperative intravenous magnesium sulfate reduced 24-hour morphine consumption by 24.4% (7.6 mg) and modestly lowered pain scores at rest and on movement, with no serious adverse effects reported.

Clinical significance

Magnesium-related pathways, including NMDA receptor antagonism, are a recognized target in multimodal, opioid-sparing analgesia. This meta-analysis is one of the main sources supporting intravenous magnesium as an anesthetic adjunct.

Key finding

Kehlet identified the surgical stress response, with its endocrine, metabolic and inflammatory cascades, as the key driver of postoperative morbidity apart from technical failures. He argued that no single intervention eliminates that morbidity, but multimodal interventions may substantially reduce it.

Clinical significance

This paper is the conceptual origin of multimodal perioperative care and of enhanced recovery. It reframed postoperative complications as a physiologic response that can be anticipated and managed.

Key finding

Across 12 cohort studies, preoperative sleep disturbances and sleep disorders were associated with chronic postsurgical pain at three months or later (r=0.13, 95% CI 0.06–0.20). The association was clearest for pain intensity and after knee arthroplasty, and grew with longer follow-up.

Clinical significance

Chronic postsurgical pain is a common long-term complication of surgery. Sleep before the operation is a measurable state that may help identify patients at risk well before they reach recovery.

Key finding

Continuous smartphone accelerometer data, collected from one week before to six months after cancer surgery, distinguished recovery trajectories. Patients with a postoperative complication, ED visit or readmission had about 40 fewer minutes of daily exertional activity than their own baseline at weeks 1 through 6.

Clinical significance

Passive data from a device patients already carry can measure physical recovery at home against each patient's own preoperative baseline. That makes recovery observable after discharge, where much of it happens.

Key finding

Wearable monitors showed that physician ambulation orders poorly reflected how much inpatients actually walked after major surgery: under the same order, daily steps ranged from 0 to 7698. Higher step counts on postoperative day 1, up to 1000 steps, were associated with lower odds of prolonged hospital stay (OR 0.63, 95% CI 0.45–0.84), with no further benefit above 1000.

Clinical significance

Early mobilization is a core recovery target that is rarely measured. Objective step counts gave a simple, early signal associated with length of stay and exposed the gap between what is ordered and what happens.

Key finding

Among 551,510 general surgery patients, 41.5% of all 30-day complications occurred after discharge, and 75% of those within 14 days. Patients with a post-discharge complication had higher rates of reoperation (17.9% vs 4.6%) and death (6.9% vs 2.0%).

Clinical significance

Much of surgical morbidity happens at home, in the period when patients have the least contact with their care team. This finding is a central argument for structured follow-up in the first two weeks after discharge.

Key finding

Cognitive decline at hospital discharge after major noncardiac surgery was common at every age (31% to 41%). At three months it persisted only in patients aged 60 and older (12.7%), and patients with cognitive decline at both time points were more likely to die within the first year.

Clinical significance

Postoperative cognitive change, studied at the time as postoperative cognitive dysfunction and now classed among the perioperative neurocognitive disorders, is a recovery outcome with prognostic weight, particularly in older adults.

Key finding

After major abdominal surgery in adults aged 60 and older, function fell most at one week. Mean recovery took 3 weeks for cognition, 3 months for daily activities and 6 months for instrumental activities; grip strength had not recovered at 6 months. At 6 months, 19% still had IADL disability, and preoperative physical conditioning and depression predicted recovery.

Clinical significance

Discharge is not the same as recovery. This cohort documented how long functional recovery takes in older adults and identified preoperative conditioning as a modifiable predictor.

Key finding

In 1218 patients aged 60 and older after major non-cardiac surgery, cognitive dysfunction was present in 25.8% at one week and 9.9% at three months, compared with 3.4% and 2.8% of controls. Age was the only risk factor for late dysfunction; intraoperative hypoxemia and hypotension were not risk factors.

Clinical significance

ISPOCD1 established that cognitive change after non-cardiac surgery is common and can persist in older adults. Studied at the time as postoperative cognitive dysfunction, it is now classed among the perioperative neurocognitive disorders and shapes how older patients are counseled before surgery.

Key finding

The StEP initiative's systematic review and Delphi consensus recommended six standardized patient-comfort endpoints for perioperative trials: pain at 24 hours (rest and movement), nausea and vomiting, a quality-of-recovery scale (QoR or QoR-15), time to gastrointestinal recovery, time to mobilization, and sleep quality.

Clinical significance

Shared endpoints make perioperative trials comparable and poolable. The inclusion of sleep quality and validated recovery scales marks the patient's own experience as a core outcome.

Key finding

A multispecialty working group recommended 'perioperative neurocognitive disorders' as the overarching term for cognitive impairment identified before or after surgery, aligned with DSM-5. It covers preexisting neurocognitive disorder, postoperative delirium, delayed neurocognitive recovery (to 30 days) and postoperative neurocognitive disorder (to 12 months).

Clinical significance

Common terminology linked to general-population classifications lets perioperative cognitive research connect with the broader dementia and cognition literature. It replaced the inconsistent use of 'postoperative cognitive dysfunction'.

Key finding

A COSMIN-based review of 35 studies evaluating 22 patient-reported outcome measures of recovery after abdominal surgery found that 74% of studies were of poor or fair methodological quality. None of the instruments met the International Society for Quality of Life Research minimum standards.

Clinical significance

Value-based surgical care depends on valid patient-reported measures of recovery. This review documents how much of that measurement foundation is still unbuilt.

Key finding

Using data from seven trials (2109 patients), days at home within 30 days of surgery (DAH30) was lower in older patients, those with poorer physical function and those with longer operations. Postoperative complications were associated with 3.0 fewer days at home after adjustment (95% CI 2.1–4.0).

Clinical significance

DAH30 combines length of stay, readmission, discharge destination and death into one outcome that patients understand and health systems can obtain from routine data.

Key finding

In 204 patients recovering from surgery, the minimal clinically important difference was 0.9 points for the QoR score, 8.0 for the QoR-15 and 6.3 for the QoR-40.

Clinical significance

A recovery score is useful only if clinicians know what size of change matters to patients. These thresholds let trials and quality programs interpret quality-of-recovery results.

Key finding

In 510 surgical patients followed for 12 months, the WHO Disability Assessment Schedule 2.0 was valid, reliable (Cronbach's alpha above 0.90) and responsive for measuring postoperative disability. Patients with new disability had longer hospital stays (6.9 vs 5.3 days) and more 30-day complications (20% vs 11%).

Clinical significance

Survival free of disability is arguably the outcome patients care about most. This validation made it measurable and has since served as the primary endpoint of major perioperative trials.

Key finding

Built from 1,414,006 patients at 393 hospitals, the universal ACS NSQIP surgical risk calculator uses 21 preoperative factors to predict eight outcomes. It discriminated well for mortality (c-statistic 0.944) and morbidity (0.816), performing as well as procedure-specific models.

Clinical significance

Patient-specific, empirically derived risk estimates support shared decision-making and informed consent. The calculator is now a widely used preoperative risk tool in the United States.

Key finding

The QoR-15, a 15-item short form of the QoR-40, showed good convergent validity (r=0.68), internal consistency (0.85), test-retest reliability (0.99) and responsiveness (effect size 1.35) in 127 patients after general anesthesia. It took about 2.4 minutes to complete.

Clinical significance

QoR-15 is now one of the standard patient-reported measures of early recovery, recommended by the StEP initiative for perioperative trials.

Key finding

In 905 adults discharged after non-elective surgery, 30 days of nurse-led virtual care with remote automated monitoring did not increase days alive at home (29.7 vs 29.5). It did detect and correct more medication errors (29.7% vs 5.5% detected) and reduced the proportion of patients reporting pain at 7, 15 and 30 days.

Clinical significance

This trial shows that structured remote follow-up after discharge is feasible at scale and changes measurable care processes. It also shows that the headline outcome a program targets must match what the program can realistically move.

Key finding

In 2084 patients having elective colorectal surgery at 80 Spanish centers, care in a self-declared ERAS center was associated with fewer moderate-to-severe complications (25.2% vs 30.3%; OR 0.77). Overall adherence was 63.6%, and the highest-adherence quartile had far fewer moderate-to-severe complications than the lowest (OR 0.34, 95% CI 0.25–0.46).

Clinical significance

Having a protocol is not the same as delivering it. Real-world adherence was incomplete even in ERAS centers, and the adherence gradient tracked outcomes.

Key finding

Across 15 academic hospitals implementing ERAS for colorectal surgery (2876 patients), only 20.1% of patients received compliant care in all phases. Postoperative elements had the poorest compliance (40.3%) yet were most strongly associated with optimal recovery (RR 2.12, 95% CI 1.81–2.47).

Clinical significance

The recovery phase is where enhanced recovery pathways most often break down and where adherence appears to matter most. Implementation effort weighted toward the preoperative and intraoperative phases leaves the largest gap unaddressed.

Key finding

System-wide ERAS implementation for colorectal surgery across six Alberta Health Services sites raised guideline compliance from 40% to 65%. Analysis of 2188 quotes from 189 documents found barriers and enablers spread across clinical practice (22%), individual providers (26%), patients (25%), organization (19%) and external environment (7%).

Clinical significance

Evidence-based protocols spread only with deliberate implementation. This study used established implementation-science frameworks (TDF and QUERI) to show where adoption succeeds or stalls, with patients accounting for a quarter of the barriers and enablers.

Key finding

As adherence to the ERAS protocol rose from 43.3% to 70.6% in 953 patients having colorectal cancer surgery, postoperative complications (OR 0.73) and symptoms (OR 0.53) fell. Adverse outcomes declined stepwise with adherence above 70%, 80% and 90%, and restriction of intravenous fluid and a preoperative carbohydrate drink were major independent predictors.

Clinical significance

This was among the first studies to show a dose-response relationship between protocol adherence and outcomes. It made measuring adherence a core part of delivering enhanced recovery.