Daily Anesthesiology Research Analysis
Three anesthesiology-relevant studies stand out today: a large international RCT (PROTHOR) shows no benefit of high PEEP with recruitment during one-lung ventilation and more intraoperative complications; an international cohort (ALICE) details the high prevalence and multifactorial etiology of preoperative anemia; and an RCT in TKA suggests liposomal bupivacaine for adductor canal block lowers pain scores and opioid use without changing the proportion with moderate-to-severe pain.
Summary
Three anesthesiology-relevant studies stand out today: a large international RCT (PROTHOR) shows no benefit of high PEEP with recruitment during one-lung ventilation and more intraoperative complications; an international cohort (ALICE) details the high prevalence and multifactorial etiology of preoperative anemia; and an RCT in TKA suggests liposomal bupivacaine for adductor canal block lowers pain scores and opioid use without changing the proportion with moderate-to-severe pain.
Research Themes
- Intraoperative ventilation strategies during one-lung ventilation
- Preoperative anemia epidemiology and etiology in major surgery
- Optimization of regional analgesia for total knee arthroplasty
Selected Articles
1. Effects of intraoperative higher versus lower positive end-expiratory pressure during one-lung ventilation for thoracic surgery on postoperative pulmonary complications (PROTHOR): a multicentre, international, randomised, controlled, phase 3 trial.
In this 28-country phase 3 RCT of 2200 thoracic surgery patients undergoing one-lung ventilation, a high PEEP plus recruitment strategy did not reduce postoperative pulmonary complications versus low PEEP without recruitment. High PEEP increased intraoperative hypotension and arrhythmias, whereas hypoxemia rescue maneuvers were more frequent with low PEEP.
Impact: This definitive trial challenges routine use of high PEEP with recruitment during one-lung ventilation by showing no clinical benefit and more intraoperative instability, informing ventilation strategies globally.
Clinical Implications: Avoid routine high PEEP with recruitment during one-lung ventilation in patients with BMI <35 kg/m2; adopt lower PEEP/permissive atelectasis with individualized rescue strategies to balance oxygenation and hemodynamics.
Key Findings
- Primary outcome (postoperative pulmonary complications) was similar: 53.6% (high PEEP) vs 56.4% (low PEEP); absolute risk difference −2.68 pp (95% CI −6.36 to 1.01); p=0.155.
- High PEEP increased intraoperative complications: hypotension 37.3% vs 14.3% and new arrhythmias 9.9% vs 3.9%.
- Hypoxemia rescue maneuvers were more frequent with low PEEP (8.8% vs 3.3%).
- No differences in extrapulmonary postoperative complications or total adverse events between groups.
Methodological Strengths
- Large, multicentre, international randomized phase 3 trial with 2200 participants.
- Modified intention-to-treat analysis and prespecified outcomes relevant to thoracic anesthesia.
Limitations
- BMI ≥35 kg/m2 patients were not included, limiting generalizability to severe obesity.
- Blinding of intraoperative ventilation strategy is not feasible, potentially introducing performance bias.
Future Directions: Evaluate individualized PEEP titration and alternative lung-protective strategies in subgroups (e.g., obesity, compromised lung function) and assess longer-term pulmonary outcomes.
BACKGROUND: The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. METHODS: In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m FINDINGS: Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference -2·68 percentage points [95% CI -6·36 to 1·01]; p=0·155). Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41-21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982). The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. INTERPRETATION: In patients with a BMI of less than 35 kg/m
2. The aetiology and prevalence of preoperative anaemia in patients undergoing major surgery (ALICE): an international, prospective, observational cohort study.
In a 79-center, 20-country prospective cohort of 2702 major-surgery patients, preoperative anemia was common (31.7%). Among those with confirmed etiologies, iron deficiency predominated (55.2%), but vitamin B12 (7.7%) and folate (14.5%) deficiencies were substantial, indicating the need for a broader workup than iron alone.
Impact: Provides granular, international evidence on preoperative anemia etiologies, supporting comprehensive patient blood management beyond iron supplementation.
Clinical Implications: Preoperative anemia screening should include iron studies as well as vitamin B12 and folate assessments; protocols should address multifactorial etiologies to optimize perioperative outcomes.
Key Findings
- Preoperative anemia prevalence was 31.7% among 2702 major-surgery patients.
- Among 782 with confirmed etiologies, iron deficiency accounted for 55.2%; vitamin B12 deficiency 7.7%; folate deficiency 14.5%; chronic kidney disease 8.7%.
- Iron deficiency was the most prevalent etiology across sex, age groups, and countries.
Methodological Strengths
- Prospective, multicentre design across 79 hospitals in 20 countries.
- Standardized definitions and broad inclusion reflecting real-world surgical populations.
Limitations
- Etiology analysis limited to a subset with confirmatory data (782/856 anaemic patients), which may introduce selection bias.
- Observational design precludes causal inference regarding outcomes or treatment effects.
Future Directions: Investigate targeted, multimodal correction pathways (iron, B12, folate, CKD management) and quantify impacts on transfusion rates and postoperative outcomes in interventional trials.
BACKGROUND: Preoperative anaemia is a major risk factor for perioperative morbidity. Because iron deficiency is widely assumed to be the main cause of anaemia in surgical patients, treatment efforts have focused mostly on iron supplementation. However, the aetiology of anaemia is multifactorial. To further understand the underlying causes and consider a comprehensive approach to anaemia management, we studied the prevalence and aetiology of preoperative anaemia in patients undergoing major surgery. METHODS: This prospective, multicentre, observational cohort study was done in 79 hospitals in 20 countries on five continents; patients were aged at least 18 years, undergoing major surgery, and had a postoperative in-hospital stay of at least 24 h. Patients donating autologous blood before surgery were excluded. Data were extracted from the electronic hospital information system and from self-reported information during preoperative examination. The primary outcomes were the prevalence of anaemia, defined as haemoglobin less than 120 g/L for women and less than 130 g/L for men, analysed in all participants, and the aetiology of anaemia, analysed only in patients with anaemia for whom aetiology could be confirmed. The study was registered with ClinicalTrials.gov (NCT03978260) and is complete. FINDINGS: Between Aug 26, 2019, and Dec 26, 2021, 2830 patients undergoing major surgery were recruited and 2702 patients were included in the analysis (1417 [52·4%] were male, 1279 [47·3%] were female, and six [0·2%] had gender dysphoria). Overall, 856 (31·7%, 95% CI 31·2-32·2) patients had preoperative anaemia. Among 782 patients with preoperative anaemia, for whom the presence of at least one aetiology could be confirmed, 432 (55·2%, 48·9-61·6) had iron deficiency, 60 (7·7%, 6·6-8·7) had vitamin B12 deficiency, 113 (14·5%, 12·2-16·7) had folate deficiency, 68 (8·7%, 8·1-9·3) had chronic kidney disease, and 48 (6·1%, 4·5-7·8) had anaemia resulting from another cause; patients could be assigned to multiple aetiologies. Across male and female sex, all age groups, and all countries, iron deficiency was the aetiology with the highest prevalence. INTERPRETATION: The prevalence of preoperative anaemia in patients in this study who were undergoing major surgery is high. Iron deficiency is the primary cause of this anaemia; however, the substantial prevalence of vitamin B12 and folate deficiencies demands immediate attention and action. FUNDING: None. TRANSLATIONS: For the Afrikaans, Albanian, Arabic, French, German, Greek, Italian, Korean, Portuguese, Romanian, Slovenian, Spanish, and Turkish translations of the abstract see Supplementary Materials section.
3. Liposomal Bupivacaine Versus Ropivacaine With Perineural Dexamethasone in Adductor Canal Block for Total Knee Arthroplasty: A Randomized Clinical Trial.
In 72 TKA patients randomized to ACB with liposomal bupivacaine vs ropivacaine plus perineural dexamethasone, the 48-hour incidence of moderate-to-severe pain with movement was not different. Liposomal bupivacaine reduced pain scores, opioid use, and improved recovery quality at 24–48 hours without increasing adverse events.
Impact: Addresses a common perioperative analgesic decision in TKA using an active comparator and patient-centered outcomes, informing cost–benefit considerations of liposomal formulations.
Clinical Implications: Liposomal bupivacaine ACB may be considered to lower pain intensity and opioid consumption and enhance recovery quality, though it may not reduce the proportion with moderate-to-severe pain at 48 hours; cost and availability should guide selection.
Key Findings
- Primary endpoint was not different: moderate-to-severe pain with movement at 48 h was 47.2% vs 63.9% (RR 0.71; 95% CI 0.43–1.16; P=0.149).
- Liposomal bupivacaine lowered NRS pain scores at rest and with movement at 24 and 48 h and reduced opioid consumption 0–24 h and 24–48 h (both P<0.05).
- Quality of recovery improved at 24 and 48 h in the liposomal group; adverse event rates were similar between groups.
Methodological Strengths
- Prospective randomized design with active comparator and prespecified patient-centered outcomes.
- Clinically relevant block (adductor canal) preserving quadriceps strength.
Limitations
- Modest sample size (n=72) may limit power for the primary endpoint and subgroup analyses.
- Short follow-up limited to 48 hours; longer-term outcomes (function, opioid-related adverse effects) not assessed.
Future Directions: Larger multicentre RCTs with cost-effectiveness analyses and longer follow-up should assess functional recovery, persistent pain, and opioid-related harms.
BACKGROUND: Adductor canal block (ACB) provides effective analgesia for knee surgery while preserving quadriceps muscle strength. However, conventional local anesthetics yield only a short-lasting effect. To extend analgesia duration and reduce opioid usage, the administration of liposomal bupivacaine and perineural dexamethasone has been proposed. The present study assessed and compared the analgesic effectiveness and duration between liposomal bupivacaine and ropivacaine with perineural dexamethasone in patients undergoing total knee arthroplasty (TKA). METHODS: A total of 72 patients scheduled for primary unilateral TKA were prospectively randomized to receive a single-injection ACB with either liposomal bupivacaine combined with bupivacaine hydrochloride (n = 36) or ropivacaine with perineural dexamethasone (control group, n = 36). The primary endpoint was the incidence of moderate-to-severe pain with movement at 48 hours postoperatively. The secondary outcomes included the incidence of moderate-to-severe pain both at rest and with movement at other time points, numerical rating scale pain score, opioid consumption, quality of postoperative recovery, and adverse events. RESULTS: At 48 hours, the incidence of moderate-to-severe pain with movement did not differ between the liposomal bupivacaine group and the control group (47.2 versus 63.9%; relative risk 0.71; 95% confidence interval: 0.43 to 1.16; P = 0.149). Patients receiving liposomal bupivacaine showed significantly lower numerical rating scale scores both at rest and with movement at 24 and 48 hours, and consumed less opioid from zero to 24 and 24 to 48 hours (both P < 0.05). Furthermore, these patients showed an improved quality of recovery at 24 and 48 hours compared to the control group (both P < 0.05). The incidence of adverse events did not differ significantly between the two treatment groups (P > 0.05). CONCLUSIONS: A single-injection ACB with liposomal bupivacaine combined with bupivacaine hydrochloride did not significantly reduce the incidence of moderate-to-severe postoperative pain with movement compared to ropivacaine with perineural dexamethasone after TKA. However, this intervention significantly decreased pain intensity scores, lowered opioid consumption, and improved recovery quality without increasing adverse events compared to the control group.