Association Between Use of Enhanced Recovery After Surgery Protocol and Postoperative Complications in Total Hip and Knee Arthroplasty in the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty Study (POWER2) | Orthopedics | JAMA Surgery | JAMA Network
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Figure 1.  STROBE Flow Diagram for Included Patients
STROBE Flow Diagram for Included Patients
Figure 2.  Postoperative Outcomes and Enhanced Recovery After Surgery (ERAS) Adherence
Postoperative Outcomes and Enhanced Recovery After Surgery (ERAS) Adherence

Patients are stratified by complications, type of complication, and other secondary outcomes and by quartile of adherence to the ERAS protocol. Surgical complications included all postoperative complications as defined by protocol17 according to the standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions,23 the standardized list, definitions, and the stratification developed by the Hip Society,24 the standarized list and definitions of the Knee Society,25 and the Standardized Bleeding Definitions for Cardiovascular Clinical Trials.26 IQR indicates interquartile range; LOS; length of stay; and OR, odds ratio.

aUnless otherwise indicated, data are expressed as number (percentage) of patients.

Figure 3.  Bubble Plot of the Rate of Postoperative Complications vs Length of Stay, Number of Participating Patients, and Rate of ERAS Program Adherence
Bubble Plot of the Rate of Postoperative Complications vs Length of Stay, Number of Participating Patients, and Rate of ERAS Program Adherence

For each hospital, the plot shows the mean percentage of adherence to the Enhanced Recovery After Surgery (ERAS) program (bubble color), the mean length of hospital stay, and percentage of patients who have postoperative complications. The bubble diameter indicates the number of patients that the hospital contributed to the study.

Table 1.  Demographic and ERAS Adherence Dataa
Demographic and ERAS Adherence Dataa
Table 2.  Multivariable and Multilevel Analysis for Postoperative Complicationsa
Multivariable and Multilevel Analysis for Postoperative Complicationsa
Supplement.

eTable 1. ERAS Compliance Definitions

eTable 2. Predefined Mild-Moderate-Severe Overall Postoperative Complications

eTable 3. Patient Characteristics by ERAS Adherence

eTable 4. Postoperative Outcomes in Patients Undergoing Total Hip Arthroplasty

eTable 5. Postoperative Outcomes in Patients Undergoing Total Knee Arthroplasty

eTable 6. Graded Postoperative Complications by Self-declared ERAS Centers or Not

eTable 7. ERAS Adherence in Patients Undergoing Total Hip Arthroplasty

eTable 8. ERAS Adherence in Patients Undergoing Total Knee Arthroplasty (Median [IQR])

eTable 9. ERAS Individual Items Adherence

eTable 10. Time to Mobilization and Feeding

eTable 11. Graded Postoperative Complications by ERAS Adherence

eTable 12. ERAS Adherence in ASA I-II and ASA III-IV Groups

eTable 13. Univariate and Multivariate Analysis for Length of Stay

eFigure 1. Postoperative Outcomes

eFigure 2. Postoperative Outcomes and Enhanced Recovery After Surgery (ERAS) Adherence in Patients Undergoing THA

eFigure 3. Postoperative Outcomes and Enhanced Recovery After Surgery (ERAS) Adherence in Patients Undergoing TKA

eFigure 4. Time to Mobilization and Feeding in All Patients Grouped by ERAS Adherence

eFigure 5. Time to Mobilization and Feeding in THA Patients Grouped by ERAS Adherence

eFigure 6. Time to Mobilization and Feeding in TKA Patients Grouped by ERAS Adherence

eFigure 7. Postoperative Outcomes and Enhanced Recovery After Surgery in All ASA I-II Patients Grouped by Self-declared ERAS Center or Not

eFigure 8. Postoperative Outcomes and Enhanced Recovery After Surgery in All ASA III-IV Patients Grouped by Self-declared ERAS Center or Not

eFigure 9. Postoperative Outcomes and Enhanced Recovery After Surgery in ASA I-II Patients Grouped by ERAS Adherence

eFigure 10. Postoperative Outcomes and Enhanced Recovery After Surgery in ASA III-IV Patients Grouped by ERAS Adherence

eFigure 11. Bubble Plot (Grouped by ERAS)

eFigure 12. Bubble Plot (THA Patients)

eFigure 13. Bubble Plot (THA Grouped by ERAS)

eFigure 14. Bubble Plot (TKA Patients)

eFigure 15. Bubble Plot (TKA Grouped by ERAS)

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    Original Investigation
    February 12, 2020

    Association Between Use of Enhanced Recovery After Surgery Protocol and Postoperative Complications in Total Hip and Knee Arthroplasty in the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty Study (POWER2)

    Javier Ripollés-Melchor, MD1,2,3,4; Ane Abad-Motos, MD1,2,3,4; Yolanda Díez-Remesal, MD, PhD5; et al Marta Aseguinolaza-Pagola, MD6; Lidia Padin-Barreiro, MD7; Rubén Sánchez-Martín, MD8; Margarita Logroño-Egea, MD9; Juan C. Catalá-Bauset, MD10; Silvia García-Orallo, MD11; Elvira Bisbe, MD, PhD12; Nuria Martín, MD13; Alejandro Suárez-de-la-Rica, PhD3,4,14; Ana B. Cuéllar-Martínez, MD4,15; Silvia Gil-Trujillo, MD16; Juan Carlos Estupiñán-Jiménez, MD17; Marta Villanova-Baraza, MD18; Cristina Gil-Lapetra, MD19; Pilar Pérez-Sánchez, MD20; Nicolás Rodríguez-García, MD21; Alvaro Ramiro-Ruiz, MD4,22; Carla Farré-Tebar, MD23; Alejandro Martínez-García, MD24; Pedro Arauzo-Pérez, MD25; Cristina García-Pérez, MD26; Alfredo Abad-Gurumeta, MD, PhD1,2,4; María A. Miñambres-Villar, MD27; Alberto Sánchez-Campos, MD28; Ignacio Jiménez-López, MD, PhD29; José M. Tena-Guerrero, MD30; Oliver Marín-Peña, MD, PhD31; Míriam Sánchez-Merchante, MD32; Ubaldo Vicente-Gutiérrez, MD33; María C. Cassinello-Ogea, MD, PhD34; Carlos Ferrando-Ortolá, MD, PhD3,4,13; Héctor Berges-Gutiérrez, MD35; Jesús Fernanz-Antón, MD36; Manuel A. Gómez-Ríos, MD37; Daniel Bordonaba-Bosque, MD, PhD38; José M. Ramírez-Rodríguez, MD, PhD3,4,38,39; José Antonio García-Erce, PhD3,4,40; César Aldecoa, MD, PhD3,4,41; for the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty (POWER2) Study Investigators Group for the Spanish Perioperative Audit and Research Network (REDGERM)
    Author Affiliations
    • 1Department of Anaesthesia and Critical Care, Infanta Leonor University Hospital, Madrid, Spain
    • 2School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
    • 3Spanish Perioperative Audit and Research Network (REDGERM)
    • 4Grupo Español de Rehabilitación Multimodal, Enhanced Recovery After Surgery Spain Chapter, Madrid
    • 5Department of Anaesthesia and Critical Care, Ramón y Cajal University Hospital, Madrid, Spain
    • 6Department of Anaesthesia, Donostia University Hospital/Donostia Unibertsitate Ospitalea, San Sebastián, Spain
    • 7Department of Anaesthesia, Complejo Hospitalario Universitario De Vigo–Eoxi Vigo, Vigo, Spain
    • 8Department of Anaesthesia, Hospital Universitario Clínico San Carlos, Madrid, Spain
    • 9Department of Anaesthesia, Hospital Universitario de Álava, Vitoria-Gasteiz, Spain
    • 10Department of Anaesthesia, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
    • 11Department of Anaesthesia, Hospital Universitario Sierrallana, Torrelavega, Spain
    • 12Department of Anaesthesia, Hospitales del Parc de Salut Mar, Barcelona, Spain
    • 13Department of Anaesthesia, Hospital Clínic de Barcelona, Barcelona, Spain
    • 14Department of Anaesthesia and Critical Care, La Paz University Hospital, Madrid, Spain
    • 15Department of Anaesthesia and Critical Care, Hospital Universitario Central de Asturias, Oviedo, Spain
    • 16Department of Anaesthesia, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
    • 17Department of Anaesthesia, Hospital Universitario Rey Juan Carlos, Móstoles, Spain
    • 18Department of Anaesthesia, Hospital de Mataró, Mataró, Spain
    • 19Department of Anaesthesia, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
    • 20Department of Anaesthesia, Hospital de Galdakao-Usansolo, Bizkaia, Spain
    • 21Department of Anaesthesia, Hospital de La Cruz Roja, Gijón, Spain
    • 22Department of Anaesthesia, Hospital Universitario 12 de Octubre, Madrid, Spain
    • 23Department of Anaesthesia, Althaia Xarxa Assistencial Universitària de Manresa, Barcelona, Spain
    • 24Department of Anaesthesia, Hospital Universitario de Jaén, Jaén, Spain
    • 25Department of Anaesthesia, Hospital Quirón, Zaragoza, Spain
    • 26Department of Anaesthesia, Hospital Universitario de Léon, Léon, Spain
    • 27Department of Anaesthesia, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
    • 28Department of Anaesthesia, Hospital Universitario de Cruces, Bilbao, Spain
    • 29Department of Anaesthesia, Hospital Universitario Virgen del Rocío, Sevilla, Spain
    • 30Department of Anaesthesia, Complejo Hospitalario de Mérida, Mérida, Spain
    • 31Department of Orthopedia, Infanta Leonor University Hospital, Madrid, Spain
    • 32Department of Anaesthesia, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
    • 33Department of Anaesthesia, Clínica Santa Cristina, Albacete, Spain
    • 34Department of Anaesthesia, Hospital Universitario Miguel Servet, Zaragoza, Spain
    • 35Department of Anaesthesia, Hospital Universitario Virgen Macarena, Sevilla, Spain
    • 36Department of Anaesthesia, Hospital Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain
    • 37Department of Anaesthesia, Complejo Hospitalario Universitario de A Coruña, Coruña, Spain
    • 38Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain
    • 39Department of Surgery, Lozano Blesa University Hospital, Zaragoza, Spain
    • 40Blood and Tissue Bank of Navarra, Servicio Navarro de Salud-Osasunbidea, Pamplona, Navarra, Spain
    • 41Department of Anaesthesia and Perioperative Medicine, Río Hortega University Hospital, Valladolid, Spain
    JAMA Surg. 2020;155(4):e196024. doi:10.1001/jamasurg.2019.6024
    Key Points

    Question  How frequent are complications after total hip and knee arthroplasty procedures and how are the Enhanced Recovery After Surgery (ERAS) protocols associated with them?

    Findings  In this large, multicenter cohort study that included 6146 patients in 131 hospitals, 680 (11.1%) presented with postoperative complications and 352 (5.7%) presented with complications graded as moderate to severe. Patients who had greater compliance with the ERAS items had fewer postoperative complications, regardless of whether or not the center had an established ERAS protocol.

    Meaning  Although only a few perioperative interventions were associated with decreased complications, greater adherence with the set of ERAS measures was associated with a decrease in postoperative complications at 30 days of follow-up.

    Abstract

    Importance  The Enhanced Recovery After Surgery (ERAS) care protocol has been shown to improve outcomes compared with traditional care in certain types of surgery.

    Objective  To assess the association of use of the ERAS protocols with complications in patients undergoing elective total hip arthroplasty (THA) and total knee arthroplasty (TKA).

    Design, Setting, and Participants  This multicenter, prospective cohort study included patients recruited from 131 centers in Spain from October 22 through December 22, 2018. All consecutive adults scheduled for elective THA or TKA were eligible for inclusion. Patients were stratified between those treated in a self-designated ERAS center (ERAS group) and those treated in a non-ERAS center (non-ERAS group). Data were analyzed from June 15 through September 15, 2019.

    Exposures  Total hip or knee arthroplasty and perioperative management. Sixteen individual ERAS items were assessed in all included patients, whether they were treated at a center that was part of an established ERAS protocol or not.

    Main Outcomes and Measures  The primary outcome was postoperative complications within 30 days after surgery. Secondary outcomes included length of stay and mortality.

    Results  During the 2-month recruitment period, 6146 patients were included (3580 women [58.2%]; median age, 71 [interquartile range (IQR), 63-76] years). Of these, 680 patients (11.1%) presented with postoperative complications. No differences were found in the number of patients with overall postoperative complications between ERAS and non-ERAS groups (163 [10.2%] vs 517 [11.4%]; odds ratio [OR], 0.89; 95% CI, 0.74-1.07; P = .22). Fewer patients in the ERAS group had moderate to severe complications (73 [4.6%] vs 279 [6.1%]; OR, 0.74; 95% CI, 0.56-0.96; P = .02). The median overall adherence rate with the ERAS protocol was 50.0% (IQR, 43.8%-62.5%), with the rate for ERAS facilities being 68.8% (IQR, 56.2%-81.2%) vs 50.0% (IQR, 37.5%-56.2%) at non-ERAS centers (P < .001). Among the patients with the highest and lowest quartiles of adherence to ERAS components, the patients with the highest adherence had fewer overall postoperative complications (144 [10.6%] vs 270 [13.0%]; OR, 0.80; 95% CI, 0.64-0.99; P < .001) and moderate to severe postoperative complications (59 [4.4%] vs 143 [6.9%]; OR, 0.62; 95% CI, 0.45-0.84; P < .001) and shorter median length of hospital stay (4 [IQR, 3-5] vs 5 [IQR, 4-6] days; OR, 0.97; 95% CI, 0.96-0.99; P < .001).

    Conclusions and Relevance  An increase in adherence to the ERAS program was associated with a decrease in postoperative complications, although only a few ERAS items were individually associated with improved outcomes.

    Introduction

    An estimated 310 million patients undergo surgery worldwide each year.1 In the United States, 1 million total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures are performed annually, with an expectation of growth in the coming years.2 The International Surgical Outcomes Study3 showed that 16.5% of patients who underwent orthopedic surgery experienced complications. The incidence of complications in THA and TKA was 3.2% to 8.0%,4 with an important variability between centers.4,5 Postoperative complications after THA and TKA have been shown to increase hospital length of stay (LOS).6 Kehlet7 described the concept of the multimodal approach to recovery in 1997. The Enhanced Recovery After Surgery (ERAS) program that entails an evidenced-based protocol based on a wide literature search was initiated by Ljungqvist et al8 in the ERAS study group, which later developed into the ERAS Society. The ERAS protocol includes a variable number of multidisciplinary perioperative measures whose initial goal is to improve recovery and reduce morbidity, which will result in secondary benefits, including reductions in LOS, convalescence, and costs.9 Observational studies10 and randomized clinical trials11 have shown that ERAS was associated with improved outcomes in patients undergoing THA and TKA, mainly a decrease in LOS.12,13

    Until the recent publication of the ERAS Society THA and TKA guidelines,14 the most accepted recommendations were those proposed by Soffin and YaDeau in 2016.15 ERAS in THA and TKA share the same problems as ERAS in other surgical procedures: adoption is slow,16 and adherence to ERAS guidelines is low.17

    The aim of this study was to characterize the management strategies for patients who underwent elective THA or TKA, including centers with and without an established ERAS protocol. The primary end point was the incidence of postoperative complications. Secondary end points were LOS and the potential associations between the adherence to the individual ERAS items and the occurrence of postoperative complications.

    Methods
    Study Design and Participants

    This study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline18 and the Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOVER) Checklist.19 Hospital and investigator engagement was facilitated through the Spanish Perioperative Audit and Research Network (REDGERM), which was established by the Grupo Español de Rehabilitación Multimodal (GERM). All hospitals in Spain were invited to participate regardless of the number of beds and the existence of an ERAS protocol.

    The Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty (POWER2) study was a prospective 2-month multicenter cohort study. The study was approved by the Instituto Aragonés de Ciencias de la Salud Ethics Committee, Zaragoza, Spain, and the Spanish Medical Agency and was registered prospectively in an international trial registry.20 The study protocol, technical appendix, and other documents are available at http://www.grupogerm.es/power2, and the study protocol has been published.21

    The ethics committees or institutional review boards at each site reviewed and approved the protocol. Written informed consent was obtained from all participants.

    Procedures

    All consecutive adult patients (aged >18 years) undergoing elective primary THA or TKA were included during a single period of recruitment from October 22 through December 22, 2018, in each participating center. Each patient was followed up for 30 days after surgery. The follow-up was performed through hospital and primary care medical records.

    Data were collected using Castor Electronic Data Capture22 and anonymized before entry onto a secure Internet-based electronic case record form designed specifically for POWER2. Participating hospitals were considered self-proclaimed ERAS centers in cases in which a multidisciplinary clinical pathway was implemented, regardless of the perioperative items that conformed to the pathway and whether hospitals were audited regularly. Individual data on 16 ERAS items were collected prospectively for each included patient. The definition of the individual ERAS components was based on the recommendations of Soffin and YaDeau15 (eTable 1 in the Supplement). Data included patient characteristics (American Society of Anesthesiologists [ASA] score, age, sex, smoking status, body mass index, clinical frailty score, and comorbidities), procedure performed, surgical approach, perioperative interventions, adherence to ERAS items, and outcomes (including postoperative complications, time to achieve targeted mobility, LOS, and 30-day mortality). Complications were defined and graded as mild, moderate, or severe according to international recommendations21,23-26 (eTable 2 in the Supplement) and were included if they occurred within 30 days after surgery. Data validation was conducted by specific validators at each site. A minimum sample size of 3012 was estimated, expecting 50% of patients with at least 1 complication, a 95% confidence level, and 3% accuracy.

    Outcomes

    The primary outcome was the number of patients with 30-day in-hospital postoperative complications. Secondary outcome measures included the number of patients with 30-day in-hospital postoperative moderate to severe complications, mortality, readmission, reintervention rates, and hospital LOS.

    Statistical Analysis

    Data were analyzed from March 15 through September 15, 2019. We analyzed outcomes depending on whether the patient received treatment at a hospital that belonged to a self-designated ERAS program (ERAS group). The discrete and continuous variables were described as number (percentage) and median (interquartile range [IQR]), respectively. We analyzed differences using the Fisher exact test for discrete variables and the Pearson and Wilcoxon rank sum tests for continuous variables. Subsequently, we repeated the analysis, subdividing the sample into quartiles according to the real adherence rate to ERAS items (regardless of whether the patient was treated at an ERAS hospital or not) and comparing the quartiles of higher and lower adherence to ERAS items. Next, we analyzed complication rates for each of the ERAS items using the Fisher exact test, and we performed a multivariable logistic regression analysis to study the association of the rate of each of the items with the clinical and demographic variables. We also used the same model in a multilevel multivariable logistic regression model to explore independent factors associated with postoperative complications assessing the variability of each site. Stratification by type of surgery (THA or TKA) was performed for the most relevant outcomes.

    We performed several post hoc analyses. To assess the association of the underlying pathologic finding in the included patients, we divided the patients between those with ASA scores of I through II and III through IV (higher scores indicate severe preoperative systemic disease) and analyzed the adherence to ERAS items in these groups, as well as the postoperative outcomes. We performed this analysis for the self-described ERAS centers vs non-ERAS centers and for the ERAS adherence quartiles, depending on the median compliance in each group. Bubble plots were used to graphically illustrate the associations between the percentage of patients with postoperative complications and LOS with the volume of patients recruited at each site. To study the association between the percentage of patients with postoperative complications and LOS and the volume of patients recruited by each center, we used 2 β regression models. Through a linear regression model, we performed a post hoc analysis to evaluate the influence of ERAS items and other perioperative variables in LOS. For this purpose, we performed a univariable and a multivariable analysis. We denoted as statistically significant those comparisons where 2-sided P < .05.

    Results
    Participants

    Data describing 6146 patients were collected in 131 hospitals in Spain (Figure 1). Of these, 2566 (41.8%) were men and 3580 were women (58.2%); median age was 71 (IQR, 63-76) years. Other characteristics are shown in Table 1. No centers or patients were excluded owing to low recruitment. According to the hospitals where the surgeries were performed, 1592 patients (25.9%) were included in self-designated ERAS centers. The ERAS and non-ERAS groups showed demographic differences in the number of patients with hypertension (2747 [60.3%] vs 900 [56.5%]), coronary artery disease (290 [6.4%] vs 70 [4.4%]), atrial fibrillation (336 [7.4%] vs 85 [5.3%]), chronic kidney disease (224 [4.9%] vs 108 [6.8%]), ASA score (ASA III-IV (345 [21.7%] vs 1273 [28.0%]), and duration of surgery (median, 90 [IQR, 75-115] vs 83 [IQR, 65-104] minutes). More patients in the ERAS group received local anesthesia (188 [11.8%] vs 64 [1.4%]) and tranexamic acid (1348 [85.9%] vs 3191 [70.2%]), whereas fewer patients in the ERAS group received epidural (38 [2.4%] vs 350 [7.7%]) or regional (157 [9.9%] vs 770 [16.9%]) anesthesia. Patients in the ERAS group also received fewer crystalloids (median, 800 [IQR, 550-1000] vs 1000 [IQR, 700-1200] mL) and colloids (median, 0 [IQR, 0-250] vs 0 [IQR, 0-0] mL) during surgery as well as fewer red blood cell transfusions (RBCTs) (mean [SD], 9 [0.6%] vs 52 [1.1%]) (Table 1). ERAS adherence quartiles were calculated for all patients from the median overall adherence to the 16 ERAS items, regardless of whether the patient was treated within an ERAS protocol. Adherence in quartile 1 was 43.75% or less; in quartile 2, greater than 43.75% to 50.00%; in quartile 3, greater than 50.00% to 62.50%; and in quartile 4, greater than 62.50%. The quartile with the lowest adherence to ERAS included the most patients (eTable 3 in the Supplement). Patients with lower adherence to ERAS had a higher prevalence of chronic kidney disease (48 [4.4%] vs 103 [5.0%]), had longer duration of surgery (median, 90 [IQR, 74-110] vs 90 [IQR, 75-115] minutes), received more crystalloid during surgery (median, 1000 [IQR, 700-1200] vs 1000 [750-1200] mL), and had more epidural anesthesia (73 [6.8%] vs 149 [7.2%]) and regional analgesia (185 [17.1%] vs 244 [11.8%]) performed compared with the group with greater adherence to ERAS (eTable 3 in the Supplement).

    Outcome Data

    A total of 680 patients (11.1%) experienced overall postoperative complications, and 352 (5.7%) experienced complications graded as moderate to severe (eFigure 1 in the Supplement). No differences were found in the number of patients with overall postoperative complications between the ERAS and non-ERAS groups (163 [10.2%] vs 517 [11.4%]; OR, 0.89; 95% CI, 0.74-1.07; P = .22) or in terms of readmission, reintervention, or survival (eFigure 1 in the Supplement). Fewer patients in the ERAS group had moderate to severe complications (73 [4.6%] vs 279 [6.1%]; OR, 0.74; 95% CI, 0.56-0.96; P = .02). eTables 4 and 5 in the Supplement show the stratified complications in THA and TKA in ERAS vs non-ERAS centers. In THA and TKA, the ERAS group had shorter median LOS (THA, 4 [IQR, 3-5] vs 5 [IQR, 4-6] days; TKA, 4 [IQR, 3-5] vs 5 [IQR, 4-6] days) (eFigure 1 and eTables 4 and 5 in the Supplement). Graduation of the severity of postoperative complications is shown in eTable 6 of the Supplement.

    ERAS Adherence and Outcome Data

    The overall adherence rate to the ERAS protocol components was 50.0% (IQR, 43.8%-62.5%), with the rate for ERAS facilities being 68.8% (IQR, 56.2%-81.2%) vs 50.0% (IQR, 37.5%-56.2%) at non-ERAS centers (P < .001). Adherence to specific ERAS items was greater in the ERAS group (Table 1). The ERAS group also had less bleeding (median blood loss, 200 [IQR, 100-400] vs 200 [IQR, 100-350] mL), less use of intraoperative crystalloids (median, 800 [IQR, 550-100] vs 1000 [IQR, 700-1200] mL), and greater intraoperative administration of tranexamic acid (1348 [85.9%] vs 3191 [70.2%]) (Table 1). In the TKA and THA procedures, adherence to perioperative ERAS items was greater in the ERAS group (eTables 7, 8, and 9 in the Supplement).

    Patients in the ERAS group undergoing THA and TKA had less time to ambulation (mean [SD] for THA, 17.2 [13.3] vs 30.9 [24.4] hours; mean [SD] for TKA, 15.2 [13.9] vs 29.1 [15.5] hours) and oral intake (mean [SD] for THA, 6.04 [5.12] vs 8.12 [11.2] hours; mean [SD] for TKA, 6.05 [5.11] vs 8.20 [6.07] hours) (eTable 10 in the Supplement). Among the highest (quartile 4) and lowest (quartile 1) quartiles of adherence to ERAS items, quartile 4 also had a decrease in the rate of overall postoperative complications (270 [13.0%] vs 144 [10.6%]; OR, 0.80; 95% CI, 0.64-0.99; P < .001), moderate to severe postoperative complications (143 [6.9%] vs 59 [4.4%]; OR, 0.62; 95%, CI, 0.45-0.84; P < .001), postoperative hemorrhage (106 [5.1%] vs 31 [2.3%]; OR, 0.44; 95% CI, 0.29-0.65; P < .001), infection of uncertain source (17 [0.8%] vs 3 [0.2%]; OR, 0.28; 95% CI,0.06-0.84; P = .02), and surgical complications (37 [1.8%] vs 12 [0.9%]; OR, 0.50; 95% CI, 0.25-0.93; P = .03) (Figure 2). Gradation of the severity of postoperative complications is shown in eTable 11 in the Supplement. eFigures 2 and 3 in the Supplement show the results grouped by THA and TKA. In THA and TKA, the highest ERAS adherence group had shorter LOS (eFigures 2 and 3 in the Supplement) and less time to ambulation and oral intake (eFigure 4 in the Supplement) in THA and TKA (eFigures 5 and 6 in the Supplement).

    Multivariable analysis of the associations with ERAS items showed a statistically significant reduction of complications in patients who had regional anesthesia (OR, 0.71; 95% CI, 0.53-0.96; P = .02) and early mobilization (OR, 0.61; 95% CI, 0.45-0.83; P = .002) (Table 2). A higher preoperative hemoglobin value (OR, 0.84; 95% CI, 0.77-0.91; P < .001) and tranexamic acid administration (OR, 0.66; 95% CI, 0.51-0.86; P = .002) were associated with fewer complications, whereas blood loss was associated with postoperative complications (OR, 1.00; 95% CI, 1.00-1.00; P < .001) (Table 2). In the multilevel study, early mobilization was associated with decreased complications (OR, 0.60; 95% CI, 0.42-0.86; P = .005) but not regional anesthesia (OR, 0.75; 95% CI, 0.54-1.05; P = .10) (Table 2).

    Stratification of adherence to individual ERAS items by severity groups showed that healthier patients had higher adherence to ERAS (eTable 12 in the Supplement). In the ERAS centers, patients with ASA scores of I to II experienced less infection of uncertain source (1 [0.1%] vs 16 [0.5%]; OR, 0.19; 95% CI, 0.01-0.91; P = .04), less hemorrhage (18 [0.1%] vs 104 [3.2%]; OR, 0.45; 95% CI, 0.26-0.73; P = .001), and lower median LOS (4 [IQR, 3-5] vs 5 [IQR, 3-6] days; OR, 0.95; 95% CI, 0.94-0.97; P < .001) compared with the non-ERAS centers (eFigure 7 in the Supplement), whereas patients with ASA scores of III to IV in the ERAS centers experienced less readmission compared with non-ERAS centers (18 [5.2%] vs 36 [28%]; OR, 1.90; 95% CI, 1.04-3.35; P = .04) (eFigure 8 in the Supplement). Regardless of belonging to a ERAS center or not, patients with ASA scores of I to II with greater adherence to ERAS had fewer moderate to severe complications (31 [3.0%] vs 79 [5.3%]; OR, 0.55; 95% CI, 0.35-0.83; P = .004) and lower median LOS (4 [IQR, 3-5] vs 5 [IQR, 4-6] days; OR, 0.97; 95% CI, 0.95-0.98; P < .001) compared with those with less adherence to ERAS (eFigure 9 in the Supplement), whereas no difference was found between patients with ASA scores of III to IV with more or less adherence to ERAS (eFigure 10 in the Supplement).

    No significant association was found among the volume of patients recruited, hospital LOS, and postoperative complications. LOS decreased a mean of 0.0048 days due to an increase in 1 patient (P = .20, associated with β regression models), whereas the increase of 1 person per center increased the postoperative complications by 0.37% (P = .10, associated with β regression models) (Figure 3 and eFigures 11-15 in the Supplement).

    Median LOS was shorter in the ERAS group compared with the non-ERAS group (4 [IQR, 3-5] vs 5 [IQR, 4-6] days; P < .001). Regarding the difference by adherence quartiles, quartile 1 presented with a median LOS of 5 (IQR, 4-6) days, compared with 4 (IQR, 3-5) days in the highest adherence group (OR, 0.97; 95% CI, 0.96-0.99; P < .001) (Figure 3). The post hoc multivariable analysis of the influence of patient characteristics and ERAS items showed a statistically significant reduction of LOS in patients who achieved early mobilization (β coefficient, −0.51; 95% CI, −0.95 to −0.06; P = .03) and received local anesthesia (β coefficient, −1.59; 95% CI, −2.61 to −0.57; P = .002), whereas active prevention of unintentional hypothermia (β coefficient, 0.78; 95% CI, 0.30-1.26; P = .001), epidural anesthesia (β coefficient, 1.53; 95% CI, 0.79-2.26; P < .001), and complications (β coefficient, 2.63; 95% CI, 2.00-3.25; P < .001) were associated with an increase in LOS (eTable 13 in the Supplement). It was not necessary to censor any P value after the multiple comparison study to adjust the false discovery rate to 5%.

    Discussion

    POWER2 examined the postoperative outcomes in patients scheduled for THA or TKA and the outcomes associated with 16 evidence-based care components of an ERAS protocol in 131 centers in Spain and more than 6000 patients without limiting the inclusion of patients to centers with an established ERAS protocol. Results demonstrated that the implementation of an ERAS protocol was associated with improved postoperative outcomes.

    A 2018 meta-analysis27 found that ERAS protocols were associated with a significant decrease in transfusions, complication rates, and LOS without decreasing mortality or increasing the 30-day readmission rate in patients undergoing THA or TKA. During the last decade, the clinical pathways and care programs in THA and TKA have undergone considerable changes in many countries influenced by the ERAS concept.28 However, in the absence of guidelines, the items that comprise these ERAS protocols were not clearly defined and present a great variability in the studies performed.27 POWER2 found that the adherence to ERAS protocol in THA and TKA was low in all patients, although it was higher and close to 70% in self-proclaimed ERAS centers. The low adherence to ERAS protocols may be owing to the usual barriers to the implementation of ERAS in other disciplines, such as resistance to change, inadequate financing, lack of administration support, high turnover, poor documentation, and lack of time,29 to which orthopedic procedures add the lack of guidelines and the economic pressure to achieve decreases in LOS.

    An adherence of greater than 62.50% was associated with a decrease in postoperative complications, including mild and moderate to severe. Importantly, only some of the perioperative interventions seemed to be associated with a decrease in complications. Similarly, Khan et al12 demonstrated that the application of an ERAS protocol based on a few components that included a multidisciplinary strategy involving patient education, multimodal analgesia, standardized perioperative anesthesia, local anesthetic infiltration, judicious fluid administration, tranexamic acid administration, and early mobilization led to a reduction in complications, LOS, and 30-day mortality. Khan et al12 showed mean hospital stays of 3 days for patients in ERAS centers, whereas in POWER2, the best results were a median of 4 days in the patients with greater adherence to ERAS. Although some centers and health systems have stays of 3 or fewer days and even perform THA and TKA as outpatient procedures, the usual LOS30 is similar to that reported in POWER2. This may be because, in Spain, patients are directly discharged home. In contrast, postacute care is typically available and covered by insurance companies in the United States and in other countries, making it easy for hospitals to discharge patients to rehabilitation facilities or to other intermediate centers.31

    POWER2 found no association between comorbidities or frailty and complications, although patients with an ASA physical status score of III had more complications. We found that in the ERAS centers and in the group with greater ERAS adherence, there were more healthy patients. This finding could explain the best results in these groups. In fact, although the ERAS programs in THA and TKA have been proven safe and beneficial for most patients, we have found that in high-risk patients (ASA scores of III-IV), the application of ERAS, even in the highest adherence quartiles, did not result in better outcomes, although there were fewer readmissions.12

    In patients undergoing major orthopedic surgical procedures, preoperative anemia, perioperative bleeding, and a liberal transfusion policy are the main risk factors for requiring an RBCT,32 which increases complications and LOS.33,34 Yang et al35 showed that in patients undergoing TKA, tranexamic acid administration reduced blood loss and the need for RBCT. Similarly, we found that lower preoperative hemoglobin values and intraoperative bleeding were associated with an increase in complications, whereas the administration of tranexamic acid was associated with a decrease. Avoiding anemia, improving tolerance to anemia, and avoiding bleeding and RBCT are the pillars of patient blood management programs.36 Surprisingly, the ERAS patient blood management item included in POWER2 has not been associated with better outcomes. In our opinion, many centers may apply the patient blood management measures without recognizing them as such.

    It is not surprising that good analgesic control leads to early mobilization, and accomplishment of these items was associated with improved outcomes. Early mobilization in the first 24 hours after THA or TKA had been shown to be effective in reducing LOS, although it had not been associated with a decrease in complications.37 Nevertheless, in POWER2, early mobilization was associated with fewer complications and shorter LOS. Conversely, epidural anesthesia was associated with a greater than 1-day increase in hospital LOS.

    Early mobilization is considered a cornerstone in ERAS pathways and is strongly recommended as part of ERAS guidelines in many surgical disciplines.8 ERAS Society guidelines recommend that patients be mobilized as soon as possible after surgery.14 Chua et al38 found that for patients undergoing THA, shorter time to mobilization was associated with hospital site and the absence of acute complications. For patients undergoing TKA, shorter time to mobilization was associated with hospital site and absence of donor blood transfusion.38 These outcomes indicate that the patient who has complications cannot move early, and delays in mobilization could be taken as an alarm signal for possible complications. However, the delay until mobilization can also be related to the institution and local protocols, because certain hospitals encourage early patient mobilization, whereas others do not.

    Strengths and Limitations

    POWER2 had several strengths compared with other studies. This was a prospective study, with a case report form designed specifically for the study and with a short recruitment period of 2 months. We also included a large number of centers. Other studies have had years-long durations.34 Khan et al12 showed that the application of an ERAS program improved outcomes in a single center and in a long period of 7 years; the changes produced in such long periods decrease patient comparability. On the other hand, some of the studies with the highest number of cases were registers in national databases, in which it is assumed that all patients were treated with an ERAS protocol, but in which the adherence was not analyzed. We have included self-described ERAS centers and non-ERAS centers, and we have analyzed the variables that make up the ERAS protocol in all the centers, unlike the studies based on databases or the before-and-after studies. Moreover, the inclusion of consecutive, nonselected patients from 131 different centers without any selection bias increases the internal validity of our study. In addition, there were few losses of follow-up.

    Our study has certain limitations. It was observational, which means that we can only obtain associations. Second, as previously mentioned, early mobilization can act as a confounding factor; because patients with complications could not fulfill this item, whether mobilization is an exposure factor or an outcome is debatable. We believe that it must be treated as both, and that all patients should be encouraged to move as soon as possible after surgery, because this has been shown to improve postoperative outcomes.39 Third, we chose the individual ERAS items based on expert recommendations15; if we had selected other items, the results might be different. On the other hand, the patients in the ERAS group probably corresponded to more specialized centers and were healthier compared with patients in non-ERAS centers, which could explain why they had better outcomes.

    Conclusions

    This study found that ERAS protocols in THA and TKA do not appear to be applied in daily clinical practice, even in self-proclaimed ERAS centers, even though a greater adherence to ERAS improves postoperative outcomes. An effective pathway for THA and TKA consists of regional or local analgesia, anemia and bleeding management, and early mobilization as the basis of the care trajectory. Consequently, our findings suggest that the focus should be on these essential elements of care rather than on expanding adherence to the other, less evidence-based components in most ERAS protocols.

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    Article Information

    Accepted for Publication: December 1, 2019.

    Corresponding Author: Javier Ripollés-Melchor, MD, Department of Anaesthesia and Critical Care, Infanta Leonor Unversity Hospital, Gran Vía del Este 80, 28031 Madrid, Spain (ripo542@gmail.com).

    Published Online: February 12, 2020. doi:10.1001/jamasurg.2019.6024

    Author Contributions: Dr Ripollés-Melchor had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Ripollés-Melchor, Abad-Motos, García-Orallo, Ferrando-Ortolá, Ramírez-Rodríguez, García-Erce, Aldecoa.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Ripollés-Melchor, Padin-Barreiro. Rodríguez-García, Ferrando-Ortolá, Bordonaba-Bosque.

    Critical revision of the manuscript for important intellectual content: Ripollés-Melchor, Abad-Motos, Díez-Remesal, Aseguinolaza-Pagola, Sánchez-Martín, Logroño-Egea, Catalá-Bauset, García-Orallo, Bisbe, Martín, Suárez-de-la-Rica, Cuéllar-Martínez, Gil-Trujillo, Estupiñán-Jiménez, Villanova-Baraza, Gil-Lapetra, Pérez-Sánchez, Ramiro-Ruiz, Farré-Tebar, Martínez-García, Arauzo-Pérez, García-Pérez, Abad-Gurumeta, Miñambres-Villar, Sánchez-Campos, Jiménez-López, Tena-Guerrero, Marin-Peña, Sánchez-Merchante, Vicente-Gutiérrez, Cassinello-Ogea, Ferrando-Ortolá, Berges-Gutiérrez, Fernanz-Antón, Gómez-Ríos, Ramírez-Rodríguez, García-Erce, Aldecoa.

    Statistical analysis: Ripollés-Melchor, Bordonaba-Bosque, Ramírez-Rodríguez.

    Obtained funding: Aseguinolaza-Pagola, Marin-Peña.

    Administrative, technical, or material support: Ripollés-Melchor, Abad-Motos, Aseguinolaza-Pagola, Padin-Barreiro, García-Orallo, Rodríguez-García, Fernanz-Antón, Ramírez-Rodríguez, García-Erce.

    Supervision: Ripollés-Melchor, Abad-Motos, Díez-Remesal, Aseguinolaza-Pagola, Padin-Barreiro, Marin-Peña, Ferrando-Ortolá, Ramírez-Rodríguez, García-Erce, Aldecoa.

    Conflict of Interest Disclosures: Dr Ripollés-Melchor reported receiving personal fees from Edwards Lifesciences and Fresenius Kabi outside the submitted work. Dr Bisbe reported receiving personal fees from Vifor Pharma outside the submitted work. Dr Abad-Gurumeta reported receiving personal fees from Merck & Co, Ferrer Pharmaceuticals, Braun PharmaCare, Panamericana Editorial, 3M Company, Rovipharm, and Altan Pharma Ltd outside the submitted work. Dr Jiménez-López reported receiving personal fees from Edwards Lifesciences outside the submitted work. Dr Marin-Peña reported receiving personal fees from Johnson & Johnson, 3M Company, and Stryker Corporation outside the submitted work. Dr Cassinello-Ogea reported receiving personal fees from Vifor Pharma outside the submitted work. Dr García-Erce reported receiving personal fees from Alexion Pharmaceuticals, Inc, Amgen, Inc, Braun PharmaCare, Celgene Corporation, Ferrer Pharmaceuticals, GlaxoSmithKline, Inmucor, Jansen Pharmaceutica, Novartis International AG, Octapharma AG, Sanofi, Sandoz, Inc, Terumo Corporation, Vifor Pharma, and Zambon and nonfinancial support from Vifor Pharma outside the submitted work. No other disclosures were reported.

    Funding/Support: This study was supported by institutional and/or departmental sources. The Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty (POWER2) study was supported by the Spanish Perioperative Audit and Research Network (REDGERM).

    Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Group Information: All researchers of the POWER2 Study Investigators Group collected data and provided care for study patients. The POWER2 Investigators Group includes the following centers and investigators: Hospital Universitario Nuestra señora de Candelaria, Santa Cruz de Tenerife: María Elena Espinosa-Domínguez (principal investigator [PI]), José L. Pozo-Gómez, and María E. Yanes-Luque (data validator) (Department of Anesthesia). Hospital Universitario de Jaén, Jaén: Alejandro Martínez-García (PI), Almudena Morales-Rojas, Ángela M. Soriano-Pérez, Enrique García-Vena, María Navío-Poussivert, Laura Rodríguez-Melguizo, Sonia Gutiérrez-Jiménez, and Juan M. Ortiz-Cortés (data validator) (Department of Anesthesia). Hospital Universitario del Sureste, Arganda del Rey: Diego Anta-Redondo (PI) and Raquel Álvarez-Manzanedo (data validator) (Department of Anesthesia). Complejo Hospitalario Universitario Insular Materno Infantil de Gran Canaria: Dolores Betancort-Gutiérrez (PI), Abraham Ortega-Ramos, Agustín Fuentes-González, Alexis Rodríguez-León, Cristina Martín-Rico, Juan José Rodríguez-Ruiz, Laura Concepción-Santana, Rut Aracil-González, Luiz Beltrame, Patricia Borrego-Ojeda, Raquel Sánchez-Nuez, Oliver Monzón-Déniz, and José Valín-Martínez (data validator) (Department of Anesthesia). Hospital Universitario La Paz, Hospital Cantoblanco, Madrid: Hanna Pérez-Chrzanowska (PI) and María D. Burgueño-González (data validator) (Department of Anesthesia). Hospital Universitario Miguel Servet, Zaragoza: María C. Cassinello-Ogea (PI), María C. Fraca-Cardiel, María P. Herranz-Andrés, and Inmaculada Gonzalo-Pellicer (data validator) (Department of Anesthesia). Consorci Sanitari del Garraf: Fernando Remartínez-Fernández (PI) and Nicolás M. Decoud-Paniagua (data validator) (Department of Anesthesia). Agencia Sanitaria Costa del Sol, Marbella: María P. Castillo-Mafla (PI) and Adrián Santos-Macías (data validator) (Department of Anesthesia). Hospital García Orcoyen, Estella. Navarra: María Remón-Izquieta (PI and data validator), Guillermo Napal-Ongay, Gabriel Cerdán-Rodríguez, and Inés Plaja-Martí (Department of Anesthesia). Hospital Juan Ramón Jiménez, Huelva: Juan V. Lorente-Olazábal (PI and data validator), Elena Benito-Ramallo, José L. Bonilla-Garcia, María D. Díaz-Lara, José M. García-García, Alejandro Gavira-Leon, Maria De-la-Peña-Gómez-Dominguez, Pablo Longo-Guridi, Marisol Hernández-del-Castillo, Irene Jarana-Aparicio, Irene Mojarro-Zamora, Cecilia Prieto-Candau, Ana M. Quintero-Moreno, and David Soriano-López (Department of Anesthesia). Hospital Universitario Quirón Dexeus, Barcelona: Sergi Alabau-Rodríguez (PI) and Ariadna Subirà-González (Department of Anesthesia); Carlomagno Cárdenas-Nylander (PI and data validator) (Department of Orthopedic Surgery). Hospital Clínico Universitario San Juan de Alicante: Jorge Hernando-Saez (PI), Sergio Tejada-Ortega, Paula Arnau-Papí, Francisco Manresa-Ballester, Javier Agulló-Agulló, Luís Such-Sánchez, Vera García-García, Carolina Fernández-Ortuño, and María José Guillamón-Marín (data validator) (Department of Anesthesia). Hospital Universitario Lucus Augusti: Maria Bermudez-López (PI and data validator), Maria López-Rodríguez, Patricia Vázquez-Dopazo, Gloria Prado-Núñez, and Carlos Villagrán-Marín (Department of Anesthesia). Complexo Hospitalario Universitario de Ourense: Leticia Gómez-Viana (PI and data validator), Olalla Figueiredo-González, David García-Quiroga, Eva López-López, Jorge Olmo-Do-Rodríguez, Ariadna Rodríguez-Rodríguez, Raquel Ruido-Dacal, and Eva Villar-Arcay (Department of Anesthesia); Roberto Casin-Bricio (Department of Orthopedic Surgery); Fernando Lamas-López (Department of Dental and Oral Medicine). Complejo Hospitalario Universitario de Pontevedra: Marina Varela-Durán (PI and data validator), Pilar Díaz-Parada, Beatriz Hernández-Vázquez, Cristina Barreiro-Pardal, Ángela González-Vilar, Marina Barreiro-Torres, and Susana Marcelo-Brage (Department of Anesthesia). Hospital General Universitario Reina Sofía, Murcia: Antonio Murcia-Asensio (PI), Abdalaziz Lanagran, Iván Morales-González, José Fernando-Moreno, Raquel Lax-Pérez, Marina Sánchez-Robles, Raúl Vilaverde-Sarabia, and Francisco Ferrero-Manzanal (data validator) (Department of Orthopedic Surgery). Hospital Universitario Sierrallana, Torrelavega: Silvia García-Orallo (PI and data validator), Carmen Martínez-Mielot, Ana Santillán-Fernández, and Milagrosa Ruiz-de-Infante (Department of Anesthesia); Melodia Molinero-Montes (Department of Orthopedic Surgey); Maialen Mozo-Segurado (Department of General Surgery). Hospital Universitario Marqués de Valdecilla, Santander: Ana Solar-Herrera (PI and data validator), M. Puerto Alcalde-Hierro, Cristina Salomón-Felechosa, María l. Sampedro-González, and Raquel Sánchez-De Arriba (Department of Anesthesia). Hospital de Viladecans: Ana Faura-Messa (PI), Augusto Gómez-Paz (PI), Vicens Rodríguez-Bustamante, and Dani López-Ruiz (data validator) (Department of Anesthesia); Marc Ramos-Villanueva (Department of Orthopedic Surgery). Hospital General de Villalba: María Fernández-Rodrigo (PI and data validator), Jenny Ballestas-Pattety, Jose L. Gracia-Martínez, Jorge L Martínez-Gómez, Carmen Mendoza-Jiménez, Juan C. Sánchez-Gil, and María E. Useche-Castañeda (Department of Anesthesia). Complejo Hospitalario de Segovia: Francisco J. García-Miguel (PI and data validator), Raquel Gómez-Sanz, Adriana S. Ramírez-Caldón, Beatriz Matji, and Pedro Román-Puche (Department of Anesthesia). Hospital General de Elda: María C. Ribera-Montes (PI), Calixto Sánchez-Pérez (data validator), Cristina Embid-Román, María V. González-Latorre, Cristina Pastor-Lain, Sergio Sánchez-Cortés, Jordi Sabater-Pavia, Aurora Rico-González, and Blanca González-Navarro (Department of Anesthesia). Hospital FREMAP Madrid: Gabriel Ruiz-Córdoba (PI and data validator), Isabel Cristóbal-García, Paula Martínez-Fariñas, and Antonio Crespo-García (Department of Anesthesia). Hospital Universitario de Fuenlabrada: Cristina Gil-Lapetra (PI), Fernando Setien-Moreno (PI), Beatriz Bolzoni-Marciel, Ana Z. Castro-Costoya, Andrea Cuadrado-Mancy, Maria I. Herrera-López, and Jose Olarra-Nuel (data validator) (Department of Anesthesia); Vicente Calzada-Exposito, Francisco J. García-Lázaro, and Carlos López-Orosa (Department of Orthopedic Surgery). Hospital Universitario de Getafe: Maria M Caro-Cascante (PI), Dolores Calles-Gato, Enrique Roca-Castillo, María J. Jiménez-García, Rocío Castellanos-González, Soledad Cortés-Mallavibarrena, Sonia Martín-Ventura, and Carmen García-Molina (data validator) (Department of Anesthesia); Segundo J. Sánchez-Gutierrez (PI) (Department of Orthopedic Surgery). Althaia Xarxa Assistencial Universitària de Manresa: Carla Farré-Tebar (PI), Francesca Reguant-Corominas, Marcelo Borderas, Montserrat Cazorla-López, Belén Gil-Calvo, Isabel Pérez-Reche, and Pere Esquius-Jofré (data validator) (Department of Anesthesia). Hospital Universitario de Basurto, Bilbao: José C. Herrero-Herrero (PI and data validator), Manuel E. Ballesteros-de-Arco, and Naiara Pérez-Vila (Department of Anesthesia). Hospital Bidasoa: Carlos Yárnoz (PI and data validator), Izaskun Emazabel (PI and data validator), María J. Asensio, Francisco J. Estomba, Itziar Murguía, and Juan R. Salmerón (Department of Anesthesia). Hospital Clínic de Barcelona: Nuria Martín (PI), Misericordia Basora, Fátima Salazar, Montserrat Tió, Adriana Martínez-Camacho, Carlos Ferrando-Ortolà, and Xavier Sala-Blanch (data validator) (Department of Anesthesia); Jenaro A. Fernández-Valencia-Laborde and Luis Lozano (Department of Orthopedic Surgery). Hospital Clínico Universitario de Valladolid: María A. Miñambres-Villar (PI and data validator), Rita P. Rodríguez-Jiménez (data validator), Sandra Fernández-Caballero, Nuria Ruiz, and Sara Cocho-Crespo (Department of Anesthesia); Ana Zabalza-Peláez and Aurelio Vega-Castillo (Department of Orthopedic Surgery). Hospital Universitario Virgen de la Salud–Toledo: Filadelfo Bustos-Molina (PI and data validator), Fátima Ortíz-Parra, María Martín-Carrillo, María Gimeno-García, María Jesús Martín-Jiménez, Paula Álvarez-Buitrago, Susana Gallardo-Sánchez, Itziar Insausti-Pacheco, Marta Torres-Montalvo, and María V. Fernández-Roldán-Galán (Department of Anesthesia). Complejo Hospitalario Universitario de Albacete: Ana Checa-Betegón (PI), Cecilia Ais-Dávila, Pedro M. Canales-Lara, Beatriz Carretero-de-la-Encarnación, Carlos Martínez-Villar, Elena Simón-Polo, and José A. Monsalve-Naharro (data validator) (Department of Anesthesia). Complejo Hospitalario de Mérida: José M. Tena-Guerrero (PI and data validator), Estefanía Palma-González (PI), and Enrique González-Sánchez (Department of Anesthesia). Complejo Hospitalario Universitario A Coruña: Manuel Á. Gómez-Ríos (PI and data validator), Eva Mosquera-Rodríguez, Sara delRío-Regueira, Sonia González-Bardanca, and Felisa Álvarez-Refojo (Department of Anesthesia). Hospital de Dénia Marina Salud: Clara Dosset-Izaguirre (PI) and Gloria Coronel-Sendra (PI and data validator) (Department of Anesthesia). Hospital General Universitario de Elche: José L. Muñoz-Rodes (PI and data validator), Raquel Flores-Mohedano, Vicent Cuquerella-Martínez, Marta Resalt-Pereira, José M. Ronda-Pérez, and Carlos Picó-Rodríguez (Department of Anesthesia). Hospitales del Parc de Salut Mar: Elvira Bisbe (PI and data validator), Sandra Aguado, Luis Carol, Carlo Moreno, and Ana Pardo (Department of Anesthesia); Alex Coello, Marc Tey, and Fernando Marques (Department of Orthopedic Surgery). Hospital Universitario de Jerez de la Frontera: Jacobo José Fedriani-de-Matos (PI and data validator), Ana Moreno-Martín, Ana Martínez-de-Castro, Elena García-Gómez, Fátima García-Herrera, María Muñoz-Zambrano, María Pérez-García, Marta Ruiz-Mayo, and María Milagrosa Santana-Pineda (Department of Anesthesia). Hospital Universitario de La Plana, Villareal: Juan C. Rivera-Gaitero (PI), Belen Poyatos-Robles, Carmen Alcalde-Sánchez, José P. Calabuig-Soler, María Á. Daras-Orenga, Montiel Redondo-Castillo, Paloma Ripollés-Martínez, and Ana Nicolau-Gozalbo (data validator) (Department of Anesthesia). Hospital de Alcañiz: Ana Maurain-Viloria (PI and data validator), Monserrat Alsina-Pujol, Pilar Igado-Insa, Patricia Calderón, and Manuel Yaya-Beas (Department of Orthopedic Surgery). Hospital Central de la Cruz Roja, San José y Santa Adela: Cristina Massa-Gómez (PI and data validator), Carmen Lope-Prado, Sonsoles Martín-Alcrudo, Julio A. Paz, Guadalupe Población-García, Luis F. Simón, and Alieriza Tabatabaian (Department of Anesthesia). Hospital Clínico Universitario de Valencia: Ana Mugarra-Llopis (PI and data validator), Estefanía Gracia-Ferrándiz, Esther Romero-Vargas, Ferran Serralta-Cabedo, and Ana Jurado-Pulgar (Department of Anesthesia). Hospital Comarcal d’Amposta: Juan Carlos Sanz-López (PI) and Estanislao Manuel-Farrés (data validator) (Department of Anesthesia). Hospital General Universitario de Ciudad Real: Silvia Gil-Trujillo (PI and data validator), Remedios Moreno-Ballesteros, Juan D. Valencia-Echeverri, Juan José Arroyo, Tatiana Castellar-Cuesta-Cabezas, and Víctor Baladrón-Gónzalez (Department of Anesthesia). Hospital Universitario La Paz: Alejandro Suarez-de-la-Rica (PI and data validator), Sofía Díaz-Carrasco, Laura Fernández-Benítez, and Almudena Martín-Martín (Department of Anesthesia). Hospital Universitario Quirón Madrid: Rocío Díez-Munar (PI and data validator) and África Fernández-Sánchez (Department of Anesthesia). Hospital Santa Clotilde de los Hermanos de San Juan de Dios: Francisco Barrios (PI and data validator) and Manuel Buitrago-Alonso (Department of Anesthesia). Hospital Universitario San Juan de Reus: Lydia Cortés-Gómez (PI and data validator) and María P. Sala-Francino (Department of Anesthesia); Marta Llauradó-Pou and Alfredo Rodríguez-Gangoso (Department of Orthopedic Surgery). Hospital Universitario de Bellvitge: María V. López-Reig (PI and data validator), Xavier Balderas-González, Javier Bocos-García, María J. Colomina-Soler, and Guillermo Puig-Sanz (Department of Anesthesia); Marcos del-Carmen, Daniel Rodríguez-Pérez, and Carles Tramunt-Monsonet (Department of Orthopedic Surgery). Hospital Universitario de Canarias: Josué Nodarse-Medina (PI and data validator), María P. Rubio-Flórez (PI), Fernando Hernández-Zayas, Paula Pineda-Bolivar, Ramón M. Orza-Muñiz, and Janet C. Hernández Chávez (Department of Anesthesia). Hospital Universitario de Móstoles: Beatriz Nacarino-Alcorta (PI and data validator), Mercedes Martínez-García (data validator) (Department of Anesthesia), Eugenio Ferrer-Santacreu (PI), and Pablo Cendrero-Cendrero (Department of Orthopedic Surgery). Hospital Universitario Sanitas La Moraleja, Madrid: Roberto Ruiz-Abascal (PI), Alfonso Moreno-Sánchez-Cañete, Amaya Moreno-Borque, Ana Argüelles-Baquero, Borja San-Pedro-de-Urquiza, David Salvatierra-Díaz, Silvia Ordóñez-Díaz, and Antonio López-del-Castillo (data validator) (Department of Anesthesia). Hospital Universitario de Burgos: Beatriz Blanco-Del-Val (PI and data validator), Sergio Bascones-Nestar, María J. Cuesta-Agudo, María I. Fernández-Martínez, María A. Gutiérrez Gómez, Ana M. Manzanal-Bañuelos, Blanca Delia-Martinez-Castro, Elena Martínez-Ibeas, María P. Isasi-Nebreda, José A Tudanca-Martínez, Juan M. de-Vicente-Lorenzo, Cristina Villalaín-Pérez, and Rodrigo Sanllorente-Sebastián (Department of Anesthesia); María E. López-Díez and María I. Mora-Fernández (Department of Orthopedic Surgery). Hospital Universitario Central de Asturias, Oviedo: Ana B. Cuéllar-Martínez (PI and data validator), Rosa A. Álvarez –Fernández (PI), Ángela García-Díaz-Negrete, Helena García-Sánchez, and Beatriz Ayuso-Iñigo (Department of Anesthesia). Hospital Universitario Infanta Cristina: Fernando Pablo Somoza-Sáez (PI and data validator) (Department of Anesthesia). Hospital Universitari Joan XXIII, Tarragona: Ana M. Fuentes-Baena (PI and data validator), María Miranda-Marín, Ione Montalvo-Aguirrezabala, Raúl Puig-Bitria, Carlos Ros-Góngora, and Judit Saludes-Serra (Department of Anesthesia). Hospital General de La Palma: Johnycar Peréz-Morales (PI), Rafael A. Omaña-García (PI and data validator), Rafael Bello-Puentes, Ana P. Castillo-German, Jerzy Tadeusz-Dwojak, Mary Ursula Irribarren-Adan, Anibal Ricardo Pérez-García, Rita C. Quiroz-Cornejo, Dieter Weingaertner, and Mauricio German-Martínez (Department of Anesthesia). OSI Alto Deba: Pablo Renedo-Corcóstegui (PI and data validator) (Department of Anesthesia). Hospital de Palamós: Diana L. Mariñansky (PI), Onel Morales-Torres (PI and data validator), Eduardo Agusti-Cobos, and Silvia Sague-Bou (Department of Anesthesia). Hospital de La Princesa, Madrid: Jara Torrente-Pérez (PI) and Enrique Alday-Muñoz (data validator) (Department of Anesthesia); Pablo Peñalver-Andrada (Department of Orthopedic Surgery). Hospital Quirón Zaragoza: Pedro Arauzo-Pérez (PI and data validator) and Paula Arauzo-Casedas (PI) (Department of Anesthesia). Hospital Universitario Rey Juan Carlos, Móstoles: Juan C. Estupiñán-Jiménez (PI), Eliomara J. Cabello-Urbina, and Irene Portero-Larragueta (data validator) (Department of Anesthesia). Hospital de Sagunto: Raúl Duplá-Pérez (PI and data validator), Rafael de-Diego-Catalá, and Marianela Martínez-Hermosilla (Department of Anesthesia). Hospital Sant Joan Deu–Palma/Mallorca: David Fabián-González (PI), Pedro José Benito-Rodrigálvarez (PI), Ana Dora-Parera, Miguel Ferrá-Verdera, Nicolás García-de-Paredes-Porro, Luis M. Marco-Alós, Luis C. Mora-Fernández, Carlos Raduan-Ripoll, Cristina Sansaloni-Perelló, José V. Torres-Pérez (data validator), and Matias J. Sastre-Nadal (Department of Anesthesia). Hospital de la Santa Creu i Sant Pau, Barcelona: Rolf Hoffmann (PI), Marisa Moreno-Bueno, Marta Argilaga-Nogués (data validator), Adrià Font-Gual, Mireia Rodríguez-Prieto, Rafael Anaya-Camacho, Victoria Baños-Lapuente, José M. Gil-Sánchez, Marc Bausili-Ribera, Rubén Díaz-Jover, María M. Felipe-Correoso, Laura Parrilla-Quíles, Silvia Barbero-Espinosa, Xavier Crusi-Sererols, Xavier Aguilera-Roig, Màrius Valera-Pertegàs, Marcos Jordán-Sales, José C. González-Rodríguez, Esther Moya-Gómez, and Sandra Huguet-Miguélez (Department of Orthopedic Surgery). Hospital Universitario Son Espases: David Fabián-González (PI and data validator), Leandro Augusto-Brogi, Irene Enriquez-Valcarcel, Neus Esteve-Pérez, Germán Gómez-Romero, Carmen Melero-Larrocha, Grineldy Mercedes-Guzman, Elena Monterroso-Garrido, and Luis C. Mora-Fernández (Department of Anesthesia). Clínica Universidad Navarra Madrid: María M. Álvarez-Fernández (PI) and Elisa Fernádez-Elias (data validator) (Department of Anesthesia). Hospital de Villajoyosa, Alicante: Alejandra Molines-Cantó (PI), Anna Grabowska, Cristina Munck, Gracia Barber-Ballester, Maria A. Korobkoff-Fernández, María A. Lengua-Egaña, María I. Tarí-Bas (data validator), and Patricia Valls-Linares (Department of Anesthesia). Hospital Universitario Virgen Macarena, Sevilla: Héctor Berges-Gutiérrez (PI and data validator), Miguel Aisa-Gasca, José D. Bautista-González, Francisco J. Carballido-Pascual, Aurora Cruz-Ortega, Jorge García-García, Beatriz Gullón-Descane, Mercedes Gutiérrez-Moreno, Liena Izquierdo-López, Yolanda Lozano-Guijarro, Estefanía Peralta-Espinosa, and Ana Rodríguez-Artacho (Department of Anesthesia). Hospital Arnau De Vilanova, Valencia: Enrique Lloria-Pons (PI and data validator), Francisco Gramuntell, José L. Carrión, and Sara Alegre (Department of Anesthesia); Inmaculada Montón and Javier García (Department of Orthopedic Surgery). Hospital De Lliria: Cristina Ruiz (PI and data validator), Jaime García, Juan Carrizo, and Miguel Á. Gil (Department of Anesthesia); Susana Moro and Daniel Herrero (Department of Orthopedic Surgery). Hospital Universitario de Cruces, Bilbao: Alberto Sánchez-Campos (PI), Xabier Ormazabal-Rementería, and Alberto Martínez-Ruiz (data validator) (Department of Anesthesia). Hospital Universitario de Álava, Vitoria-Gasteiz: Margarita Logroño-Ejea (PI and data validator), Alaitz Urtiaga-Urrestizala, Erika Olea-De-La-Fuente, and Lucía Pérez-De-Albeniz-Vesga (Department of Anesthesia); Alexis I. Fernández-Juan, Borja López-Hernando, Luis Á. Minguez-Cabeza, and Jorge Guadilla-Arsuaga (Department of Orthopedic Surgery). Hospital de Sant Joan Despí Moisès Broggi: Jesús Fernanz-Antón (PI), Lucía Gil-Gómez, and Sandra Marmaña-Mezquita (data validator) (Department of Anesthesia); Xavi Bial-Vellvé and Carlos X. Rojas-Coutto (Department of Orthopedic Surgery); Carlos Jericó-Alba (Internal Medicine). Hospital del Dos de Maig: Sandra Marmaña-Mezquita (PI and data validator) (Department of Anesthesia); Borja García-Torres and Vicente J. López-Pérez (Department of Orthopedic Surgery). Consorci Corporació Sanitària Parc Tauli, Sabadell: Anna Peig-Font (PI and data validator), Andrea Vallejo-Tarrat, Estefanía Rabaneda-Romero, Silvia Juncà-Martí, and Laura Ricol-Lainez (Department of Anesthesia); Albert Soler-Cano, Christian Yela-Verdú, Juan Peñalver, and Vanesa Ros-Munne (Department of Orthopedic Surgery); Helena Costa and Francisco Zamora-Carmona (Nursery). Hospital Universitario Donostia/Donostia Unibertsitate Ospitalea: Marta Aseguinolaza-Pagola (PI and data validator), Ainhoa Aginaga-Badiola, Alazne Enparantza-Aiestaran, Rebeca Alcalde-León, Ane López-Montecelo, Anna Coll-Triquell, Belén-Barandiaran-Benito, Berta Catellano-Paulis, Ibonne Barceló-Zarraga, Elena del-Val-Peciña, María J. Goenaga-Álvarez, Manuel Eced-Sanchez, Nagore Echeverria-Rodríguez, Nuria González-Jorrín, Olga Cengotita-Blanco, and Ainhoa Garmendia-Odriozola (Department of Anesthesia). Hospital Universitario Fundación Alcorcón: Míriam Sánchez-Merchante (PI and data validator), Alma M. Espinosa-Moreno, Patricia Gaite-de-Vicente, Santiago García-del-Valle-y-Manzano, Livia Gisbert-de-la-Cuadra, Anna Katarzyna Grzanka, Violeta M. Heras-Hernando, Beatriz Martín-Vaquerizo, Alfredo Plaza-Mardomingo, Roberto Real-Valdés, and Pablo Redondo-Martínez (Department of Anesthesia). Hospital Universitario Rio Hortega, Valladolid: Cesar Aldecoa (PI and data validator), Irene García-Saiz, Eduardo Santos, Daniel Almudi, Clara Bolaños, and Borja Morales (Department of Anesthesia). Hospital Universitario Ramón y Cajal, Madrid: Yolanda Diez-Remesal (PI and data validator), Alberto José Balvis-Balvis, Alberto Berruezo-Camacho, Inés de-la Hoz-Polo, Borja Hinojal-Olmedillo, Sara Martín-Burcio, María C. Martín-González, and Marta Ramírez-González (Department of Anesthesia). Hospital Ernest Lluch Calatayud: Leticia I. Pérez-Pascual (PI and data validator) and Marta Ortiz-Enciso (Department of Anesthesia); Alfredo Á. Rodríguez-León and María T. Domínguez-Ayesa (Department of Orthopedic Surgery). Hospital Universitario Dr Peset, Valencia: Jorge Bellver (PI), Joana Baldó, Cristina Álvarez, Concepción Barrachina, José M. Castillo (data validator), José Higueras, Estefanía Martínez-González, María J. Molina, Leticia Narváez, Oscar Ramírez, Fernando Rauer, María T. Richart, Amparo S. de-Merás, Cyntia Sánchez-Martín, and Luisa Sapena (Department of Anesthesia). Hospital Universitario de Cáceres: Juan M. Redondo-Enríquez (PI and data validator), Francisco B. Amador-Penco, Antonio Barba-Orejudo, Inés de-Tena-Rocha, Marta Donoso-Domínguez, Laura Fuentes-Coco, Fernando García-Montoto-Pérez, Yasmina González-Marín, Luis G. Smith-Vielma, Álvaro San-Antonio-Gil, Pedro Fernández-Nuñez, and José I. Hermoso-Martínez (Department of Anesthesia). Hospital Universitario De Cabueñes: Javier Albaladejo-Magdalena (PI and data validator), Ana Rodríguez-Morala and Javier Carbayo-Lázaro (Department of Anesthesia). Clínica Santa Cristina, Albacete: Ubaldo Vicente-Gutiérrez (PI and data validator) (Department of Anesthesia), Jésus Martínez-Casrtroverde and Eduardo Rodriguez-Vellando-Rubio (Department of Orthopedic Surgery). Clinica HLA Vistahermosa: Jesús J. Mas Martinez (PI and data validator) and Javier Sanz-Reig (PI) (Department of Orthopedic Surgery); Enrique Cardenas-Alegría (Department of Anesthesia). Complejo Asistencial De Zamora: Ana M. García-Sánchez (PI and data validator), María Gómez-Fernández, Ana M. Lafuente-Lera, and Gema Martínez-Ragüés (PI) (Department of Anesthesia); Gonzalo Humada-Álvarez and Camino Román-Dopazo (Department of Orthopedic Surgery). Complejo Hospitalario Universitario de Badajoz: Maria D. Torrado-Criado (PI and data validator), Laura Caperote-Anchez, Juan R. Caro-González, Francisco S. Castaño-García, Ana Marín-Moreno, Gema Montero-Mejías, and Cristina Pinilla-Silva (Department of Anesthesia); Rafael Lorente-Moreno (data validator) (Department of Orthopedic Surgery). Complejo Hospitalario Universitario De Vigo–Eoxi Vigo: Lidia Padin-Barreiro (PI and data validator), María I. Vidal Lopo, Iván Areán-González, María A. Gil-Campelo, Pedro Martínez-Guitián, José R. Reparaz-Andrade, and Gerardo Baños-Rodríguez (Department of Anesthesia). Hospital De La Cruz Roja, Gijón: Nicolás Rodríguez-García (PI and data validator) (Department of Anesthesia); Daniel García-Rodríguez (PI) (Department of Orthopedic Surgery). Hospital Universitario de Gran Canaria Doctor Negrín: Ángel Becerra-Bolaños (PI and data validator), Aurelio Rodríguez-Pérez, Iván M. Beirutti-Ruiz, Carmen Arachelly-Focaccio-Tejada, Julio Gómez-Marrero, Leonardo Cabrera-Ramírez, and Mutaz Mourad-Mohamed (Department of Anesthesia). Hospital Don Benito Vilanueva: Marta López-Marqués (PI), María P. Rodríguez-Chaparro, Enrique Del-Cojo-Peces (data validator) (Department of Anesthesia). Hospital El Bierzo: Sergio Núñez-Moreno (PI), Sarai Suárez-Fernández, and Irene Ruperez-San-Emeterio (data validator) (Department of Anesthesia); Marta Novoa-Cortiñas and Alicia Sánchez-Parada (Department of Orthopedic Surgery). Hospital De Galdakao-Usansolo: Pilar Pérez-Sánchez (PI and data validator), Claudia Velasco-Oficialdegui, Fernado Jáuregui-Beraza, Pilar Macua-Biurrun, Raquel Malanda-Callejo, and Aizpea Aguirrezabal-Juaristi (Department of Anesthesia). Hospital General de Granollers: Germán Moreno-Aguilar (PI and data validator), Carmen Sanabria-Pico, and Regina Sopena-García (Department of Anesthesia). Hospital General Universitario Gregorio Marañón, Madrid: Roberto de-Diego-Fernández (PI), Alba Burgos-Santamaría, Carmen Corbella-Jiménez (data validator), Elena de-la-Fuente-Tornero, Elena González-Benito, Fernando Higuero-Cantonero, David Martínez-Gascueña, Ángeles de-Miguel-Guijarro, Ana G. Pizarro-Calderón, Mercedes Power-Esteban, Usamah Rabih-Kanji, Olalla Varela-García, Juan M. de-Vicente-Peña, and Santiago García-Hernández (Department of Anesthesia). Hospital Universitario de Guadalajara: Mercedes Cabellos-Olivares (PI), Laura M. Martínez-Meco (PI), and José R. Rodríguez-Fraile (data validator) (Department of Anesthesia). Hospital Universitario 12 de Octubre, Madrid: Álvaro Ramiro-Ruiz (PI and data validator), Pablo García-Pimentel, Sergio García-Pérez, Noelia González-Rabadán, Adrián Martínez-López, Teresa Martínez-Marivela, Belinda Montalbán-Moreno, Noelia Zurera-Plaza, Rubén Salas-Rodríguez, Claudia Sarrais-Polo, and Claudia Olea-Vielba (Department of Anesthesia). Hospital d’Igualada: Laura Perelló-i-Cerdà (PI), Josep M. Bausili-Pons (data validator), Ana B. Pedregosa-Sanz, Ana M. Pedrero, and Joaquim Sabater-Recolons (Department of Anesthesia). Hospital Universitario Infanta Leonor, Madrid: Javier Ripollés-Melchor (PI), Ane Abad-Motos (PI), Beatriz Nozal-Mateo, Rut Salvachua-Fernández, Alfredo Abad-Gurumeta, Elena Sáez-Ruiz, Eugenio Martínez-Hurtado (data validator), Elena Lucena-de-Pablo, Elena Nieto-Moreno, and Norma Aracil-Escoda (Department of Anesthesia); Oliver Marín-Peña (PI) and David Murillo-Vizuete (Department of Orthopedic Surgery); Elena Sánchez-Pérez (Nursery). Hospital General Universitario de Castellón: José M. España-Pamplona (PI and data validator), Laura Jordá-Sanz, María Vellida-Vilarroig, and María I. De-Miguel-Cabrera (Department of Anesthesia). Hospital Universitario Clínico San Carlos, Madrid: Rubén Sánchez-Martín (PI and data validator), Jesús Hurtado-Martín, Jhon López-Hormiga, Julián A. Vargas-Ardila, Karina Martins-Cruz, Lourdes Durán-Giménez-Rico, and Rosalía Navarro-Pérez (Department of Anesthesia). Fundacio Salut Emporda – Hospital De Figueres: Manel Roig-Gasull (PI and data validator), María del Mar Piazuelo, and Carlos Salazar-Zamorano (Department of Anesthesia). Consorcio Hospital General Universitario de Valencia: Juan C. Catalá-Bauset (PI), Rafael Colomina-Rodriguez (data validator), Lorenzo Hernádez-Ferrando, Pablo Rodríguez-Gimillo, Raquel Moratalla-García, Elena Biosca-Pérez, María Olivas-Dols, Lucas Rovira-Soriano, Rubén Rubio-Haro, Francisco Gil-Chaves, Francisco Jara-García, and Jorge Ubeda-Pascual (Department of Anesthesia). Hospital Manises: Aurora Moreno-Gazquez (PI), Raquel Viñedo-Lillo, Óscar Torres-Rico, and Vicente R. Chisbert-Cuenca (Department of Anesthesia). Hospital Municipal de Badalona: Eduard Siles-Fuentes (PI), Ester Mora-Solé, and Javier González-López (data validator) (Department of Orthopedic Surgery). Hospital Quirón de Marbella y Hospital Quirón Campo de Gibraltar: Blas Rodriguez-Gil (PI and data validator), Belén Castillo-Cardona, Raimundo Escudero-Concha, Mathieu Juvin-Bouvier (PI), and José Romero-Aguilar (Department of Anesthesia). Hospital Quirónsalud Torrevieja: Andrej Balík (PI and data validator), Noelia Ruiz-Vera, Julio P. Vinuesa-Núñez, and Ana B. Tovar-López (Department of Anesthesia). Hospital Universitario San Agustín, Avilés: Diana de-la-Uz-Díaz (PI), Paz Alonso-Pérez (data validator), Juan R. Artamendi-Suárez, Jesús Bujarrabal-Martínez, Lorena España-Fuente, Ángel Gómez-Martín, María J. González-Miranda, Covadonga Gutiérrez-González, Beatriz Laserna-Cocina, Marta López-Pérez, Andrea Manzano-Patallo, Gabriel Mella-Pérez, Rosa E. Méndez-Redondo, Marina Rodríguez-Rodríguez, Cristina M. Rodríguez-Rodríguez, Laura Morante-Carrión, and Pablo de-la-Rica-Fernández (Department of Anesthesia). Hospital Universitari Mútua Terrassa: Marga Novellas-Canosa (PI) (Department of Anesthesia); Francesc Anglès-Crespo (PI and data validator) (Department of Orthopedic Surgery). Hospital Universitario Severo Ochoa, Leganés: Vanesa Blázquez-Calvo (PI), Luis Fuentetaja-Martín-Portugués, Patricia Lloreda-Herradón, Adela Gardeta-Pallarés, Soraya Gholamian-Ovejero, Raquel González-Velasco, Adolfo Ramos-Luengo, Marta Vicente-Orgaz, Purificación Sánchez-Zamora, and Gema Fraga-Casais (data validator) (Department of Anestesia); Hilario Miguez-Pérez (Department of Orthopedic Surgery). Hospital Universitari i Politècnico la Fe de Valencia: Lucia Cabezudo-de-la-Muela (PI and data validator), Beatriz Castel-González, Daniel Martínez-Català, and María D. Ruiz-Boluda (Department of Anesthesia). Hospital Clínico Universitario Lozano Blesa de Zaragoza: Aurora Callau-Calvo (PI), Patricia García-Consuegra, and Javier Longás-Vailén (data validator) (Department of Anesthesia); José M. Ramírez-Rodríguez (Department of General Surgery). Hospital de Mataró: Marta Villanova-Baraza (PI and data validator), Roser Torruella-Turró, Raquel Algilaga-Segovia, Isabel Fábregas-Blanco, Maria Farolera-Bonamusa, Elisa Reñé-de-Antonio, Alexia Nebot-Galindo, and Cassandra Gimeno-Grauwinkel (Department of Anesthesia). Hospital Medina del Campo: María T. Fernández-Martín (PI and data validator), Juan C. Álvarez-López, Beatriz Cano-Hernández, and Christian Bravo-Ovadia (Department of Anesthesia). Hospital Universitario de Torrejón: Elena García-Fernández (PI and data validator), Sergio Lorrio-Palomino, Jesús Recio-Pérez, and José M. Requena (Department of Anesthesia). Hospital Nuestra Señora del Prado, Talavera de la Reina: Pablo Gimeno-Fernández (PI and data validator), José L. Gómez-Agraz, Carla Iglesias-Morales, Patricia Ordoñez-Díaz, Hilda L. Quispe-Melendez, Joselvy Rodríguez-Pinto, Patricia Sabin-Gutierrez, Yolanda Sarabia-Mora, and Elzbieta Stasiak-Pikula (Department of Anesthesia). Hospital Universitario Puerta de Hierro Majadahonda: Lucía Ormaechea-Bolado (PI and data validator), Guillermo Arespacochaga-Ramos, Marina Carmona-Prieto, Fernando Herva-Pintor, Ana Lacaba-Mazarío, and Javier Martínez-Caridad (Department of Anesthesia); Teresa Beteta-Robles, Beatriz Fernández-Maza, Marta Isabel Sanz-Pérez, and Marta Yáguez-Hernández (Department of Orthopedic Surgery). Quiron Teknon Barcelona: Adriana Bataller-Bassols (PI and data validator), Milen Bonev-Bonev, Amparo Gómez-Mantecon, Karen Salazar-Loaiza, and Josep Rodiera-Olivé (Department of Anesthesia); Diego Collado-Gastalver, Rafael González-Adrio, Ferran Montserrat-Ramon, David Roca-Romalde, and Miquel Sales-Pérez (Department of Orthopedic Surgery). Hospital Ruber Internacional. Madrid: Uxío García-Aldao (PI), Judit Benítez, Pilar Bernad, Álvaro Elícegui, Daciano Gaona, Isabel Gómez, Álvaro de-la-Vega, Juan P. Von-Walter, and Javier de-Benito (data validator) (Department of Anesthesia). Hospital Universitari de Santa Maria, Lleida: Jordi Colomina-Morales (PI and data validator), Isabel Parada-Avendaño (Department of Orthopedic Surgery); Reis Drudis-Morell (PI) and Montserrat Torra-Riera (Department of Anesthesia). Hospital de Zumarraga, OSI Goierri Alto Urola: Sandra L. Muñoz-Pérez (PI and data validator), Iñaki Roa-Martínez, Angel Beriain-Arcelus, Maitane Rubio–de-Jesús, and Marco Amambal-Altamirano (Department of Anesthesia). Hospital Universitario Lucus Augusti: María Bermúdez-López (PI and data validator), María López-Rodríguez, Carlos Villagrán-Marín, Gloria Prado-Núñez, and Patricia Vázquez- Dopazo (Department of Anesthesia). Complejo Asistencial Universitario de León: Cristina García-Pérez (PI and data validator), Sergio Marcos-Contreras, Javier Ferrero-de-Paz, and Diana Fernández-García (Department of Anesthesia). Servicio Navarro de Salud-Osasunbidea, Pamplona, Navarra: José A. García-Erce (PI) (Blood and Tissue Bank). Hospital MAZ Zaragoza: Clara Marín-Zaldívar (PI and data validator) and Amagoia Fernández-de-Gamarra-Goiricelaya (Department of Anesthesia); Julian C Segura-Mata (PI), Juan F Blanco-Gómez, Carlos M Enseñat-Schulte, Silvia Gomez-Gomez, Maria Llorens-Eizaguerri, Lucia Lopez-Sagasta, and Jesus Rivas-Felice (Department of Orthopedic Surgery). Hospital Universitario de Vic: Jordi Serrat-Puyol (PI and data validator), Teresa Planella-Rius, and Julio Roza-Baglietto (Department of Anesthesia); Laia Boadas-Gironés and Daniel Estevez-Sabogal (Department of Orthopedic Surgery). Hospital Universitario Fundación Jiménez Díaz, Madrid: Patricio J Amaro-Soto, Philipp Peter-Granacher, Raquel García-Ortega, Raquel Iglesias-Guitian, Fernando López-Arias, and Soledad Bellas-Cotan (PI and data validator). Hospital Virgen de los Lirios, Alcoy: José Luis Jover-Pinillos (PI), Vicente Climent-Peris, and José Pedro García-Belmonte (data validator). Hospital Universitario Príncipe de Asturias, Alcalá de Henares: Carmen Demartini-Foj (PI and data validator), Fernando Poveda-Sáenz, and Francisco Barrios (Department of Anesthesia). Hospital Universitario Infanta Elena, Valdemoro: Rubén Casans-Frances (PI and data validator), Thais Martinez-Mejia, Enrique Golderos, and Elena Del-Hierro (Department of Anesthesia); Francisco J. Cervero, Elena Galvez, Elena Villarrubia, Rodrigo Anton, Pablo Vadillo, Daniel López-Dorado, Raquel Serrano, Rocío Mascaraque, and Hugo Garlito (Department of Orthopedic Surgery). Hospital del Poniente, El Ejido: Miguel Martínez-Espinosa (PI and data validator) and Alberto Albert-Ullibarri (Department of Orthopedic Surgery). Hospital Universitario Virgen del Rocío: Juan Sánchez-Peña, Maria de los Ángeles Luengo-Pastor, Manuel Sariego-Ortiz, Jesús Fernández-López, Juan Miguel Pérez-de-Tudela, Juan Francisco Gómez-Curiel, Manuel Agustín Castro-Marín, Alvaro Sosa-Orts, Francisco Manzano-Capitán, Rosana Guerrero-Domínguez, Francisco Bullón-Barrera, Inmaculada Jimeno-Puche, Francisco Polonio-Enríquez, Lucia Romero-Escalante, Ana Martínez-Saniger, Concepción Martínez-Torres, and Ignacio Jiménez-López (PI and data validator) (Department of Anesthesia).

    Additional Contributions: Julián Álvarez Escudero, MD, PhD, President of the Spanish Society of Anesthesiology and Critical Care (SEDAR) provided a noncompensated prerecruitment announcement of the study on the SEDAR website. Alejandro Bona Enguita, BS, served as the POWER2 website webmaster. No financial compensation was provided.

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