Impact of sedation and analgesia during noninvasive positive pressure ventilation on outcome: a marginal structural model causal analysis

Abstract

Purpose

There are limited data available about the role of sedation and analgesia during noninvasive positive pressure ventilation (NPPV). The objective of study was to estimate the effect of analgesic or sedative drugs on the failure of NPPV.

Methods

We studied patients who received at least 2 h of NPPV as first-line therapy in a prospective observational study carried out in 322 intensive care units from 30 countries. A marginal structural model (MSM) was used to analyze the association between the use of analgesic or sedative drugs and NPPV failure (defined as need for invasive mechanical ventilation).

Results

842 patients were included in the analysis. Of these, 165 patients (19.6 %) received analgesic or sedative drugs at some time during NPPV; 33 of them received both. In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95 % confidence interval 0.6–5.4) or sedatives (odds ratio 2.8, 95 % CI 0.85–9.4) alone was not associated with NPPV failure, but their combined use was associated with failure (odds ratio 5.7, 95 % CI 1.8–18.4).

Conclusions

Slightly less than 20 % of patients received analgesic or sedative drugs during NPPV, with no apparent effect on outcome when used alone. However, the simultaneous use of analgesics and sedatives may be associated with failure of NPPV.

Introduction

Noninvasive positive pressure ventilation (NPPV) is an effective technique that can avert side effects and complications associated with endotracheal intubation [1]. The tolerance of NPPV is crucial for its success. Mask intolerance because of pain or discomfort, or claustrophobia, may lead the patient to refuse ongoing NPPV prompting its discontinuation. In one trial, mask intolerance or inadequate patient cooperation led to intubation in 9 % of patients with acute respiratory failure [2]. Thille et al. [3] found that up to 13 % of patients with acute respiratory failure had poor tolerance to NPPV from the beginning of ventilatory support. In a survey of 70 intensive care units (ICUs) [4] to evaluate the use of NPPV, multiple regression analysis revealed that the severity (estimated by Simplified Acute Physiology Score, SAPS II) and de novo respiratory failure were two independent predictors of the need for mechanical ventilation, whereas good tolerance to NPPV and high body mass index were associated with success. On the other hand, delirium and agitation are serious complications in critically ill patients and, even if it is indicated, NPPV is sometimes unsuccessful under these conditions [5].

For those reasons, after considering other factors known to improve adaptation of the patient to NPPV, the use of sedation during NPPV can be part of a strategy designed to optimize its use. An international survey regarding current sedation practices during NPPV in patients with acute respiratory failure showed that among physicians, 41 % used sedation and 48 % analgesic therapy for NPPV in the USA, whilst 24 % used sedation and 35 % used analgesic therapy in Europe [6]. Pilot studies suggest that continuous infusion of a single sedative agent may decrease patient discomfort, with no significant effects on respiratory drive, respiratory pattern, or hemodynamics [7]. While the current limited data available suggests that sedation during NPPV is safe and feasible, more widespread application should await the results of larger observational studies or randomized clinical trials.

Therefore, the purpose of this analysis was to assess the effect of analgesic and/or sedative drug therapy on NPPV failure.

Materials and methods

Patients

We used data from a prospective, international, multicenter, observational study of mechanically ventilated patients in 322 ICUs from 30 countries (see “Appendix 1”) throughout March 2010 (Clinicaltrials.gov identifier NCT01093482) [8]. The research ethics board of each participating institution approved the protocol and need for informed consent was according to local rules. From this data set we included patients who received more than 2 h of NPPV as first-line ventilatory support at ICU admission. We excluded those with short duration of NPPV (N = 327, of whom 72 patients failed and were intubated) to guard against reverse causality; we felt that in this short time frame it would be impossible to separate patients given sedation or analgesia because they were already failing NPPV from those given sedation or analgesia to improve comfort of ongoing NPPV.

Protocol

We collected the following baseline characteristics: age, sex, severity at ICU admission estimated by SAPS II, use of NPPV at home, application of NPPV in the hospital previous to admission in the ICU; reason for NPPV [chronic obstructive pulmonary disease (COPD), asthma, other chronic pulmonary disease non-COPD, postoperative acute respiratory failure, acute respiratory distress syndrome, community-acquired pneumonia, hospital-acquired pneumonia, congestive heart failure, aspiration, neurologic disease, trauma, sepsis, do-not-intubate order, other reason] that, for the purpose of the analysis, was grouped into three categories: hypercapnic respiratory failure, hypoxemic respiratory failure, and other; arterial blood gases prior to NPPV commencement; interface and ventilator used to apply the NPPV. At NPPV commencement we registered the following variables: mode of ventilation, inspiratory positive airway pressure, expiratory positive airway pressure, tidal volume, respiratory rate, inspired fraction of oxygen, arterial blood gases and level of consciousness-sedation by Richmond Agitation Sedation Scale (RASS) [9]. At each change of ventilator settings we registered the same variables and the administration of sedatives (midazolam, propofol, lorazepam, dexmedotimidine) or analgesics (morphine, fentanyl, remifentanyl, sufentanyl) at this moment. Monitoring was continued until NPPV was considered failed or the patient was discharged from the ICU.

The failure of NPPV was defined as the need for intubation and invasive mechanical ventilation.

Statistical analysis

Data are expressed as mean (standard deviation), median (interquartile range), absolute and relative frequencies as appropriate. Student’s t, Mann–Whitney, ANOVA, and Kruskal–Wallis tests were used to compare continuous variables and Chi-squared tests were used for categorical variables.

To assess the relationship between the use of analgesics or sedatives drugs with the failure of NPPV and to avoid time-dependent confounders, we performed a marginal structural model (MSM) by inverse probability treatment weight (IPTW) introducing analgesics, sedatives, or both as a dummy variable using non-sedoanalgesia as the reference, and adjusted by baseline variables (age, SAPS II, reason for starting NPPV, interface for NPPV), and time-dependent confounders (RASS score, pH, and PaCO2). A full description of this statistical analysis is available in the electronic supplementary material.

To account for patients clustering, the effect of analgesics or sedatives drugs on 28-day mortality was analyzed using logistic regression model with generalized estimating equations methods [10]. In the multivariable analysis for risk of mortality, we adjusted only for baseline variables related to mortality (age, SAPS II, reason for NPPV).

Statistical tests were two-sided, and p < 0.05 was considered to be statistically significant. These analyses were performed using Stata/IC 13.1 (STATA Corp, Texas, USA).

Results

At admission in the ICU, 1169 patients received NPPV. For the purpose of the current analysis we excluded 327 patients (27.9 %) because they underwent less than 2 h of NPPV.

From the remaining 842 patients, 165 patients (19.6 %) received some kind of analgesic and/or sedative drugs at any time during NPPV: 88 patients received analgesia, 44 patients received sedation, and 33 patients received both analgesics and sedatives drugs (Fig. 1). Midazolam and morphine were the most commonly used sedative and analgesic drugs. Table 1 displays the differences between patients who received analgesic and/or sedative drugs and patients who did not.

Fig. 1

Flowchart of outcome according to sedoanalgesia status. NPPV Non-invasive positive pressure ventilation

Table 1 Baseline characteristics of patients according to sedoanalgesia status during ventilatory support

Relationship between sedation–analgesia and failure of NPPV

Patients who received analgesic or sedative drugs had similar duration of NPPV—analgesics [median 24 h (interquartile range 13–85)], sedatives [median 29 h (interquartile range 11–77)], and analgesics and sedatives [median 39 h (interquartile range 7–58)]—to those who received neither [median 26 h (interquartile range 12–59)] (p = 0.938).

Overall, 269 of 842 patients (32 %) failed NPPV. Table 2 shows the differences between patients with successful NPPV and NPPV failure. Patients who failed NPPV had higher severity of illness at ICU admission, and more commonly had hypoxemic respiratory failure.

Table 2 Comparison between patients with success of noninvasive positive pressure ventilation and patients with noninvasive positive pressure ventilation failure

In the unadjusted analysis analgesia was not significantly associated with failure of NPPV (Table 3). After adjusting for confounders, the marginal structural model by IPTW analysis showed that neither analgesia (odds ratio 1.8, 95 % confidence interval 0.6–5.4) nor sedation (odds ratio 2.8, 95 % CI 0.85–9.4) was significantly associated with NPPV failure. However, the simultaneous use of analgesics and sedatives was significantly associated with failure of NPPV: odds ratio 5.7, 95 % CI 1.8–18.4 (Table 3). A full description of the development of the model is showed in ESM.

Table 3 Effect of sedoanalgesia on failure of noninvasive positive pressure ventilation

Clinical outcomes

ICU length of stay was longer in patients who received sedative drugs with analgesics [median 6 days (interquartile range 3.5–10 days)] or without analgesics [median 7 days (interquartile range 4–18 days)] vs. those who did not receive drugs [median 5 days (interquartile range 3–10 days)]. Patients who received only analgesia had a length of stay in the ICU [median 6 days, interquartile range 3–10 days) similar to patients who did not receive any drug.

Crude 28-day mortality was higher in patients who received analgesic or sedative drugs compared with those who did not (34 vs. 23 %, p = 0.014). The combination of analgesics and sedative drugs during NPPV remained significantly associated with 28-day mortality after adjustment for confounders: odds ratio 4.6, 95 % CI 2.1–9.9 (Table 4). Also, crude ICU mortality was higher (31 vs. 21 %, p = 0.007).

Table 4 Relationship between sedoanalgesia and 28-day mortality in patients with noninvasive positive pressure ventilation

Discussion

In this study, we did not find any evidence suggesting a benefit of sedation or analgesia during NPPV. Almost 20 % of patients received analgesic or sedative drugs.

A cross-sectional Web-based survey [6] carried out by American and European physicians concluded that most physicians infrequently use sedation and analgesic therapy for acute respiratory failure patients receiving NPPV, but practices differ widely within and among specialties and geographic regions. According to this survey, sedation was usually administered as an intermittent intravenous bolus, outside of a protocol. A benzodiazepine alone was the most preferred (33 %), followed by an opioid alone (29 %). Europeans were less likely to report using a benzodiazepine alone (25 vs. 39 %, p < 0.001) but more likely to report using an opioid alone (37 vs. 26 %, p < 0.009). In our study, which examined recorded actual practice, rather than stated practice patterns, we did not observe significant differences between regions.

Aside from that survey, a few clinical trials, mostly with small sample sizes and varying results, have evaluated the efficacy of analgesic or sedative drugs during NPPV [11]. Several studies [7, 12–16] have reported the evolution of a few patients—with acute respiratory failure [7, 12, 13] or failure of NPPV due to agitation [13], discomfort [14], or interface intolerance [15]—who were sedated with sufentanyl [7], morphine and/or midazolam [12], remifentanyl [13, 16], dexmedetomidine [14], or propofol [15] to obtain a level of sedation to improve the tolerance to NPPV. In these studies, the rate of intubation ranged between 0 and 39 %. Only three studies [17–19] were randomized controlled trials that compared sedation with two different drugs: midazolam vs. dexmedetomidine. Senoglu et al. [17] did not report any failure of 40 uncooperative patients sedated that received NPPV. Huang et al. [18] included 62 patients with acute cardiogenic pulmonary edema who refused NPPV and reported an overall rate of failure of 32 %, and the group assigned to midazolam had a higher rate of NPPV failure (45 vs. 21 % in the dexmedetomidine group). Devlin et al. [19] randomized 36 adults with acute respiratory failure within 8 h after starting NPPV to receive dexmedetomidine, to maintain a Sedation-Agitation Scale score of 3–4, or placebo up to 72 h. They found that initiating dexmedetomidine soon after NPPV initiation did not improve NPPV tolerance: odds ratio 1.44, 95 % CI 0.44–4.70 (p = 0.54).

Our study represents the largest observational study in patients in NPPV receiving analgesic and/or sedative drugs. We observed a rate of unsuccessful NPPV in patients who received analgesic or sedative drugs in the range of previous reports (39 %). Using a marginal structural model, we showed an independent association between the use of combined sedation or analgesia during NPPV and NPPV failure. This potentially deleterious effect of simultaneous use of analgesic and sedative drugs on outcome of critically ill patients receiving NPPV has not previously been reported [20]. Nevertheless, randomized clinical trials are encouraged to further address this question.

Our study has several limitations. First, we cannot know if the administration of sedoanalgesia drugs was used as an attempt to improve the tolerance to NPPV, or to avoid the failure of NPPV when first signs of poor tolerance appeared. Nevertheless, we think that our findings support the conclusion that the administration of sedoanalgesia, whatever the indication, did not improve the outcome of NPPV. Second, as a result of the design of the study, we did not register any variable related to the assessment of the tolerance to NPPV or to patient–ventilator interaction. Third, owing to the characteristics of this observational and non-interventional study, there was no protocol for analgesic or sedation drug dosing and we only collected the drugs administered but not their dosage. Four, the decision to start and finish NPPV was based on the clinical judgment of the physician in charge of the patients; however, this study represents the routine clinical practices in the use of NPPV in the ICU. Last, there are probably remaining unmeasured confounders. In observational studies, the control of confounding is a fundamental problem in analyzing data and interpreting results. A confounder variable is associated with both the occurrence of the outcome event (failure of NPPV) and the treatment (sedation and/or analgesia). Use of standard regression models for the analysis of cohort studies with time-updated measurements may result in biased estimates of treatment effects if time-dependent confounders affected by prior treatment are present. If past treatment predicts the current covariate value (e.g., if the covariate is on the causal pathway between treatment and the outcome), standard survival analyses with time-updated treatment effects will give biased treatment effect estimates. We have performed a marginal structural model to analyze the results of this observational study to avert time-dependent confounders. The results evaluated by the MSM are valid only under the assumption that all covariates influencing the use of NPPV were introduced in the analysis [21]. However, we included numerous measured covariates but the assumption of positivity would have not been fulfilled. The use of truncated weight would attenuate this limitation [22].

In conclusion, we observed no benefit of the use of sedation or analgesia in patients receiving noninvasive positive pressure ventilation. The association of sedation and analgesia may be related to NPPV failure.

Appendix 1: Investigators in the Third International Study on Mechanical Ventilation (2010)

Argentina: Coordinators: Fernando Ríos (Hospital Nacional Alejandro Posadas), Damian Violi (Hospital Hospital Interzonal General de Agudo Profesor Dr. Luis Guemes, Haedo)

Marisol Rodríguez-Goñi, Roger Lamoglie and Fernando Villarejo (Hospital Nacional Profesor A. Posadas, Buenos Aires); Norberto Tiribelli and Santiago Ilutovich (Sanatorio de la Trinidad, General Mitre); Matías Brizuela and Mariana Monllau (Hospital Tránsito Cáceres de Allende, Córdoba); Fernando Saldarini and Silvina Borello (Hospital General de Agudos donación Francisco Santojanni, Buenos Aires); Alberto Marino and Norberto Tiribelli (Hospital Churruca-Visca, Buenos Aires); Mauricio Vinzio and Karina Bonasegla (Sanatorio de la Trinidad, San Isidro); Julián Hernández and María Belén Yapur (Sanatorio Nuestra Señora del Rosario, Jujuy); María Eugenia González (Hospital Privado de Comunidad, Mar del Plata); Sebastián E. Mare (Sanatorio Dr. Julio Méndez, Buenos Aires); Judith Sagardía and Marco Bezzi (Hospital General de Agudos P. Piñeiro, Buenos Aires); Cecilia Pereyra and Julian Strati (Hospital Interzonal General de Agudo Profesor Dr. Luis Guemes, Haedo); Daniel Vargas and Claudia Diaz (Hospital Pablo Soria, Jujuy); Pablo Gómez and Marcelo Palavecino (Sanatorio Juncal, Temperley); Graciela Elizabeth and Aguilera García, M. Eugenia (Hospital de San Luis); Luis Pablo Cardonnet and Lisandro Betttini (Hospital Provincial del Centenario, Rosario); Hernán Nuñez and Lucas Vallejo (Hospital General de Agudos Juan A. Fernández, Buenos Aires); Fernando Fernández and Jorge Arroyo (Hospital Central, Mendoza); Daniel Duarte and Gerardo Filippa (Hospital Regional Río Grande, Tierra del Fuego); Cayetano Galetti and Hernan Nunia (Sanatorio Allende, Córdoba); Fernando Lambert and Elisa Estenssoro (Hospital Interzonal de Agudos San Martin, La Plata); Marina Busico and Fernando Villarejo (Clínica Olivos, Vicente López); Javier Horacio Álvarez (Hospital Universitario Austral, Pilar); Alejandro Raimondi and Gustavo Badariotti (Sanatorio Mater Dei, Buenos Aires); Martín Lugaro (Sanatorio Las Lomas, San Isidro); Fernando Lipovestky (Clínica Santa Isabel; Buenos Aires); Alan Javier Zazu and Hugo Capponcelli (Clínica Privada de Especialidades de Villa María); Patricia Vogl and Cristina Orlandi (Hospital Zonal Francisco López Lima, General Roca); Alejandro Gómez and Gustavo Jannello (Sanatorio de los Arcos; Buenos Aires); Alejandro Risso (Sanatorio Otamendi y Miroli, Buenos Aires); Leticia Rapetti and Guillermo Chiappero (Hospital Universitario, Universidad Abierta Interamericana, Buenos Aires); Juan Domingo Fernández (Hospital Regional de Comodoro Rivadavia, Chubut); Rodrigo E. Gómez-Paz (Hospital Español, Buenos Aires); Marcos Juan Zec and Pascual Valdez (Hospital General de Agudos Dalmacio Vélez Sársfield, Buenos Aires); Jorgelina Guyon, Ariel Chena (Hospital Lagomaggiore, Mendoza); Sergio Lasdica (Hospital Municipal Coronel Suárez, Buenos Aires); Martin Deheza, Schimdt Alejandra (Hospital General de Agudos Bernardino Rivadavia, Buenos Aires); Francisco Criado (Hospital Naval Puerto Belgrano, Bahía Blanca); Norma Beatriz Márquez (Policlínico Atlántico del Sur, Ríos Gallegos); Pablo Desmery and José Luis Scapellato (Sanatorio Anchorena, Buenos Aires); Gonzalo Javier Ríos and Cristian Casabella (Clínica Bazterrica, Buenos Aires)

Australia: Coordinators: Jasmin Board and Andrew Davies (Alfred Hospital, Melbourne)

Andrew Bersten, Elisha Matheson, and Amy Waters (Flinders Medical Center, Adelaide); John Santamaria and Jennifer Holmes (St Vincent’s Hospital, Melbourne); Cartan Costello, Manoj K. Saxena and John Myburgh (St George Hospital, Sydney); Ellen Kinkel and Forbes McGain (The Western Hospital, Melbourne); Claire Cattigan and Allison Bone (Barwon Health, Geelong Hospital, Geelong); Ian Seppelt, Leonie Weisbrodt, and Cheryl Cuzner (Nepean Hospital, Sydney); Christopher MacIsaac, Deborah Barge, and Tania Caf (Royal Melbourne Hospital, Melbourne); Cameron Knott and Graeme Duke (The Northern Hospital, Melbourne); Imogen Mitchell, Helen Rodgers, Rachel Whyte, and Elisha Fulton (Canberra Hospital, Canberra); Jasmin Board, Andrew Davies, and Alistair Nichol (Alfred Hospital, Melbourne); Hergen Buscher, Priya Nair, and Claire Reynolds (St Vincent’s Hospital, Sydney); Simon J.G. Hockley, Ian Moore, and Katherine Davidson (Calvary Wakefield Hospital, Adelaide), David Milliss, Raju Pusapati, and Helen Wong (Concord Hospital, Sydney); Jason Fletcher and Julie Smith (Bendigo Hospital, Bendigo); Paul Goldrick, Dianne Stephens, and Jane Thomas (Royal Darwin Hospital, Darwin); Anders Aneman, Sutrisno Gunawan, and Tom Cowlam (Liverpool Hospital, Liverpool); George Lukas and Rick McAllister (Royal Hobart Hospital, Hobart); Minka Springham, Joanne Sutton, and Jeff Presneill (Mater Health Services, Brisbane); Tony Sutherland and Dianne Hill (Ballarat Health Services, Ballarat); Howard Connor, Jenny Dennett, and Tim Coles (Central Gippsland Hospital, Sale).

Bolivia: Coordinator: Freddy Sandy (Hospital Obrero No.1, La Paz)

Sando Chavarria and Marcelo Choque (Hospital Obrero No.1, La Paz), Ronald Pairumani and Juan Guerra (Instituto Gastroenterológico, La Paz)

Brazil: Coordinator: Marco Antônio Soares Reis (Hospital Universitário São José, Belo Horizonte)

José Carlos Versiani (Hospital Madre Teresa, Belo Horizonte); Eduardo Fonseca Sad (Hospital Luxemburgo, Belo Horizonte); Maria Aparecida Braga (Hospital Dia e Maternidade Unimed-BH; Belo Horizonte); Dinalva Aparecida Gomes (Hospital Vera Cruz, Belo Horizonte); Fernando Antônio Botoni (Hospital de Pronto Socorro Risoleta Tolentino Neves, Belo Horizonte); Maurício Meireles Góes (Hospital da Baleia, Belo Horizonte); Frederico Costa Val Barros (Hospital da Polícia Militar, Belo Horizonte); Rogério de Castro Pereira (Hospital Felício Rocho, Belo Horizonte); Hugo Urbano (Hospital Vila da Serra, Belo Horizonte); Valéria de Carvalho Magela (Hospital Santa Rita, Contagem); Aline Camile Yehia (Hospital Júlia Kubitschek, Belo Horizonte); Bruno Bonaccorsi Fernandino (Hospital São Francisco-Setimig, Belo Horizonte); Marco Antônio Ribeiro Leão (Hospital São João de Deus, Divinópolis); Rovílson Lara (Hospital Arnaldo Gavazza Filho, Ponte Nova); Rovílson Lara (Hospital São João Batista, Viçosa); Rubens Altair Amaral de Pádua (Hospital Vaz Monteiro, Lavras); Janine Dias Alves (Santa Casa de Misericórdia de Ouro Preto, Ouro Preto); Aloísio Marques do Nascimento (Hospital Nossa Senhora das Graças, Sete Lagoas); Bruno do Valle Pinheiro (Hospital Universitário da Universidade Federal de Juiz de Fora, Juiz de Fora); Carlos Alberto Studart Gomes (Hospital de Messejana, Fortaleza); Marcelo Alcântara Holanda (Hospital Universitário Walter Cantídio, Fortaleza); Frederico Rodrigues Anselmo (Hospital Nossa Senhora Aparecida, Belo Horizonte).

Canada: Coordinator: Niall Ferguson (Mount Sinai Hospital and University Health Network, Toronto)

Neill Adhikari, Damon Scales, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, and Nicole Marinoff (Sunnybrook Health Science Centre, Toronto); Lauralyn McIntryre, Shawna Reddie, Laura Jones, and Irene Watpool (Ottawa Hospital, Ottawa); Jeffrey Singh and Madison Dennis (Toronto Western Hospital, Toronto); Andrea Matte, Marc Lipkus, and Ryan Albert (Toronto Hospital Western Division, Toronto); Andrew Steel and Emily Stern (Toronto General Hospital, Toronto); Michael Miletin, Antonio Raso, and Robyn Klages (William Osler Health Science Centre, Brampton); Jan Friedrich, Orla Smith, and Laura Wilson (St Michael’s Hospital, Toronto); Deborah Cook and Mark Bailey (St Joseph’s Hospital, Hamilton); Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, and Samer Haj-Bakri (Mount Sinai Hospital, Toronto); Dietrich Henzler and Lisa Julien (Queen Elizabeth II Health Sciences Centre, Halifax).

Chile: Coordinator: Luis Soto-Román (Instituto Nacional del Tórax, Santiago)

Juan Carlos Maurelia (Hospital de Copiapo); César Antonio Maquilon (Instituto Nacional del Tórax, Santiago); Luis Soto-Germani (Hospital de Coquimbo).

China: Coordinator: Bin Du (Peking Union Medical College Hospital, Beijing)

Yan Kang and Bo Wang (West China Hospital, Chengdu); Fachun Zhou and Fang Xu (Chongqing Medical University 1st Hospital, Chongqing); Haibo Qiu and Yi Yang (Southeast University Zhongda Hospital; Nanjing); Qingyuan Zhan and Bing Sun (Beijing Chaoyang Hospital, Beijing); Zhenjie Hu and Bin Yu (Hebei Medical University 4th Hospital, Shijiazhuang); Xi Zhu and Yu Bai (Peking University 3rd Hospital; Beijing); Gang Li and Yi Li (Sino-Japanese Friendship Hospital, Beijing); Geng Zhang and Jianbiao Meng (Zhejiang Tongde Hospital; Hangzhou); Xiaobo Huang and Hong Pu (Sichuan Provincial Hospital; Chengdu); Bin Du and Daxing Yu (Peking Union Medical College Hospital, Beijing); Chuanyun Qian and Wei Zhang (Kunming Medical College 1st Hospital, Kunming); Yongjie Yin and Debiao Song (Jilin University 2nd Hospital, Changchun); Yunxuan Yue and Zhengxuan Lv (Kunming City 3rd People’s Hospital, Kunming); Chengmin Yu and Qunmei Yao (Yunnan Chuxiong People’s Hospital; Chuxiong); Xue Wang (Xi’an Jiaotong University 1st Hospital; Xi’an); Yuan Xu and Wei He (Beijing Tongren Hospital, Beijing); Mian Chen and Zhihua Hu (Hainan Medical College Hospital; Haikou); Dongpo Jiang and Jian Huang (Daping Hospital, Chongqing); Wei Yu (Yantai Yuhuangding Hospital; Yantai); Juanxian Gu (Zhejiang Haining People’s Hospital, Naining); Yangong Chao (Beijing Huaxin Hospital, Beijing); Zhixiang Li (Fengrun District People’s Hospital; Tangshan); Zhicheng Zhang (PLA Navy General Hospital, Beijing); Wanxia Li (Nanchang University 2nd Hospital, Nanchang); Zhenyang He (Hainan Provincial People’s Hospital, Haikou); Jianguo Li and Chang Liu (Wuhan University Zhongnan Hospital, Wuhan); Tiehe Qin and Shouhong Wang (Guangdong General Hospital, Guangzhou); Feng Li (Nantong 1st People’s Hospital, Nantong); Jun Jin and Jianhong Fu (Suzhou University 1st Hospital, Suzhou); Hongyang Xu (Wuxi Municipal People’s Hospital, Wuxi); Hongyuan Lin and Jianying Guo (PLA 304 Hospital, Beijing); Yalin Liu and Jinghua Wang (Beijing Hospital, Beijing); Maoqin Li and Jiaqiong Li (Xuzhou Central Hospital, Xuzhou); Lei Chen (Sun Yet-Sen University 6th Hospital, Guangzhou); Qing Song and Liang Pan (PLA General Hospital, Beijing); Xianyao Wan and Jiuzhi Zhang (Dalian Medical University 1st Hospital, Dalian); Weihai Yao and Yuhong Guo (Beijing TCM Hospital, Beijing); Pang Wing Yan (Prince Margaret Hospital, Hong Kong); Kelly Choy (Queen Elizabeth Hospital, Hong Kong); Kwan Ming Chit (Pamela Youde Nethersole Eastern Hospital, Hong Kong); Patricia Leung (Prince Of Wales Hospital, Hong Kong); Chau Chin Man (North District Hospital, Hong Kong)

Colombia: Coordinator: Marco González (Clínica Medellín and Universidad Pontificia Bolivariana, Medellín)

Ricardo Buitrago (Clínica Shaio, Bogotá); Marcela Granados (Clínica Fundación Valle Lili, Cali); Guillermo Ortiz (Hospital Santa Clara, Bogotá); Cesar Enciso (Grupo Cimca Hospital San José, Bogotá); Mario Gómez (Grupo Cimca Hospital San José and Clínica Fundadores, Bogotá); Bladimir Alejandro Gil (Clínica Las Américas, Medellín); Juan Pablo Sedano, Luis Fernando Castro Castro (Centro Medico Imbanaco, Cali); Carlos Alberto Acosta (Hospital Federico Lleras Acosta, Ibague); Marco Gonzalez A.(Hospital San Rafael, Itagui); Francisco Molina (Clínica Universitaria Bolivariana, Medellín); Camilo Pizarro (Fundación cardiovascular colombiana, Bucaramanga); Mario Villabon (Grupo Cimca Hospital de Suba, Bogota); Carmelo Dueñas (Nuevo Hospital Bocagrande, Cartagena de Indias); Carlos Andrés Díaz (Hospital General de Medellín); Nelson Fonseca (Corbic, Medellín); Rubén Camargo (Clínica General del Norte, Barranquilla), Juan David Uribe (Clínica Cardiovascular, Medellín)

Denmark: Coordinator: Hans-Henrik Bülow (Holbak)

Simona Beniczky and Jens Brushoj (Naestved); Mikkel Præst (Nykobing Falster); Birgitte Viebaek and Sine Wichman (Roskilde); Anette Mortensen (Holbak); Susanne Andi Iversen (Slagelse); Bo Broberg (Koge)

Dominican Republic: Edgard Luna (Hospital Universitario José María Cabral y Báez, Santiago)

Ecuador: Coordinator: Manuel Jibaja (Hospital Militar de Quito)

Leonardo Pazmiño, Katty Trelles, and Fabricio Picoita (Hospital Eugenio Espejo, Quito); Gustavo Paredes and Vanesa Ramírez (Hospital Enrique Garcés, Quito); Guillermo Falconí, Cristian Cevallos, and Boris Villamagua (Hospital Carlos Andrade Marín, Quito); Marco Escobar and Freddy Sánchez (Hospital de la Policía, Quito); Miguel Llano and Miguel Lazcano (Hospital General de las Fuerzas Armadas, Quito); Ramiro Puetate and José Miguel Guerrero (Hospital Pablo Arturo Suárez, Quito); Mijail Játiva and Myriam Montalvo (Hospital de los Valles, Quito); Franklin Villegas (Hospital Metropolitano, Quito); Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, and Luis Gonzalez Mosquera (Hospital Luis Vernaza, Guayaquil); Henry Caballero and María Fernanda García (Hospital de SOLCA, Quito); Marcelo Ochoa, Soraya Puertas, and Jackeline Coello (Hospital José Carrasco Arteaga, Cuenca); Mario Acosta (Hospital San Vicente de Paul, Ibarra).

Egypt: Medhat Soliman (Cairo University Hospitals, Cairo)

France: Coordinator: Arnaud W. Thille (CHU Henri Mondor, Créteil)

Achille Kouatchet and Alain Mercat (CHU d’Angers); Laurent Brochard (CHU Henri Mondor, Créteil); François Collet (Centre Hospitalier De Saint-Malo); Guillaume Marcotte (Hôpital Édouard Herriot, Lyon); Pascal Beuret (Centre Hospitalier De Roanne); Jean-Christophe M. Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, and Fabien Soulis (CHU Charles Nicolle, Rouen); Frédéric Bellec (Centre Hospitalier De Montauban); Philippe Berger (Centre Hospitalier de Châlons en Champagne); Dorothée Carpentier, Benoit Veber (CHU Charles Nicolle, Rouen); Salem Ould Zein, Géraldine Dessertaine (CHU De Grenoble); C. Canevet (Hôpital d’Armentières); Fabien Grelon (Centre Hospitalier Du Mans).

Germany: Coordinator: Konstantinos Raymondos ( Medizinische Hochschule Hannover)

Rolf Dembinski and Rolf Rossaint (Universitaetsklinikum Aachen); Steffen Weber-Carstens (Charité Universitaetsklinikum, Berlin); Christian Putensen (Universitaetsklinikum Bonn); Maximillian Ragaller (Universitaetsklinikum Carl Gustav Carus, Dresden); Michael Quintel (Universitaetsklinikum der Georg-August-Universitaet, Goettingen); Winfried Schubert (Carl-Thiem-Klinikum Cottbus gGmbH); Thomas Bein and Heinrich Paulus (Klinikum der Universitaet Regensburg); Walter Brandt (Universitaetsklinikum, Magdeburg); Lutz Pfeiffer and Silke Frenzel (Hufeland Klinikum GmbH, Mühlhausen); Thoralf Kerner and P. Kruska (Allgemeines Krankenhaus Harburg, Hamburg); Leila Eckholt and Joachim Hartung (Vivantes Krankenhaus am Urban, Berlin-Kreuzberg); Harald Fritz and Monika Holler (Staedtisches Krankenhaus Martha-Maria Halle-Doelau gGmbH); Johannes Busch and Andreas Viehöfer (Evangelisches Waldkrankenhaus Bad Godesberg gGmbH, Bonn); Jens Buettner (Evangelisches Krankenhaus Elisabethenstift gGmbH, Darmstadt); Jörn Schlechtweg and Achim Lunkeit and Roland Schneider (Klinikum Bad Salzungen GmbH); Maria Wussow, Nils Marquardt, and Christian Frenkel (Staedtisches Klinikum Lueneburg); Falk Hildebrandt (Dietrich-Bonhoeffer Klinikum Neubrandenburg); Tumbass Volker and Thomas Lipp (Ermstalklinik Bad Urach); Cezar Mihailescu and Thomas Moellhoff (Katholische Stiftung Marienhospital Aachen); Thomas Steinke (Universitaetsklinikum der Martin-Luther-Universitaet Halle-Wittenberg); Oliver Franke and Marcus Ruecker (Lungenklinik Heckeshorn, Berlin); Markus Schappacher and Steffen Appel (Ermstalklinik Staedtisches Krankenhaus Sindelfingen); Heinz Kerger (Evangelisches Diakoniekrankenhaus, Freiburg); Andreas Schwartz (Bundeswehrkrankenhaus Ulm); Jan Dittmann and Jörg Haberkorn (Georgius-Agricola-Klinikum Zeitz); Wolfgang Baier (St. Nikolaus-Stiftshospital GmbH, Andernach); Walter Seyde (Staedtisches Klinikum Wolfenbuettel)

Greece: Coordinator: Dimitros Matamis (Papageorgiou Hospital, Thessaloniki)

Eleni Antoniadou (Gennimata Hospital, Thessaloniki); Pertsas Evangelos (Agios Pavlos General Hospital, Thessaloniki); Maria Giannakou (Ahepa Hospital, Thessaloniki).

Hungary: Zoltan Szentkereszty (Kenezy Hospital, Debrecen); Zsolt Molnar (University of Szeged)

India: Coordinator: Pravin Amin (Bombay Hospital Institute of Medical Sciences, Mumbai)

Farhad N. Kapadia (Hinduja Hospital, Mumbai); Nagarajan Ramakrishnan (Apollo Hospitals, Chennai); Deepak Govil (Artemis Health Institute, Gurgaon Haryana); Anitha Shenoy and Umesh G (Kasturba Medical College, Manipal); Samir Sahu (Kalinga Hospital, Odisha); Sheila Nainan Myatra (Tata Memorial Hospital, Mumbai); Subhash Kumar Todi (AMRI Hospitals Kolkata, West Bengal); Sanjay Dhanuka (CHL Apollo Hospital, Indore); Mayur Patel (Saifee Hospital, Mumbai); P. Samaddar (Tata Main Hospital, Jamshedpur); Dhruva Chaudhry (PGIMS, Rohtak); Vivek Joshi and Srinivas Samavedam (CARE Hospitals,Surat); Ankur Devendra Bhavsar (Spandan Multispeciality Hospital, Vadodar); Prachee Sathe (Ruby Hall Clinic, Pune); Sujoy Mukherjee (Calcutta Medical Research Institute (CMRI), Kolkat)

Italy: Coordinator: Salvatore Maurizio Maggiore (Policlinico “Agostino Gemelli”, Università Cattolica Del Sacro Cuore, Rome)

Francesco Idone and Federica Antonicelli (Policlinico “Agostino Gemelli”, Università Cattolica Del Sacro Cuore, Rome); Paolo Navalesi, Rosanna Vaschetto and Arianna Boggero (Ospedale Maggiore Della Carità, Università Del Piemonte Orientale “Amedeo Avogadro”, Novara); Rosalba Tufano, Michele Iannuzzi and Edoardo De Robertis (Ospedale Policlinico “Federico II”, Università Di Napoli, Napoli); Romano Tetamo and Andrea Neville Cracchiolo (Ospedale “Arnas Civico, Di Cristina, Benfratelli”, Palermo), Antonio Braschi, Francesco Mojoli and Ilaria Curro’ (ICU 1, Fondazione IRCCS Policlinico “S. Matteo”, Università Di Pavia, Pavia); Mirko Belliato, Chiara Verga and Marta Ferrari (ICU 2, Fondazione IRCCS Policlinico “S. Matteo”, Università Di Pavia, Pavia); Erika Mannelli, Valerio Mangani and Giorgio Tulli (Ospedale “San Giovanni Di Dio”, Firenze); Francesca Frigieri and Armando Pedulla’ (Ospedale “Santa Maria Annunziata”, Firenze); Monica Rocco, Giorgia Citterio and A. Di Russo (Policlinico “Umberto I”, Università La Sapienza, Rome); Gaetano Perchiazzi and Loredana Pitagora (Ospedale Policlinico, Università Di Bari, Bari); Antonio Pesenti and Michela Bombino (Ospedale “San Gerardo”, Università Di Milano Bicocca, Monza); Davide Chiumello, Federica Tallarini and Serena Azzari (Fondazione IRCCS “Cà Grande” Ospedale Maggiore Policlinico, Università Di Milano, Milano); Antonina Pigna, Ivano Aprile, and Marco Adversi (Policlinico Universitario “S. Orsola-Malpighi”, Bologna); Antonio Corcione, Marianna Esposito, and Annunziata Mattei (Ospedale “V. Monaldi”, Napoli); Vito Marco Ranieri, Rosario Urbino, and Ilaria Maria Mastromauro (Ospedale “San Giovanni Battista - Molinette”, Università Di Torino, Torino); Antonino Giarratano, Maurizio Raineri Santi, and Ambrogio Sansone (Policlinico “P. Giaccone”, Università Di Palermo, Palermo)

Japan: Toru Katani (Tokyo Women’s Medical University)

Korea: Coordinator: Younsuck Koh (Asan Medical Center, University of Ulsan, Seoul)

Moo Suk Park (Hospital Severance, Yonsei University Health System, Seoul); Je Hyeong Kim (Hospital Korea University of Ansan); Kyung Chan Kim (Hospital Catholic University of Daegu); Hye Sook Choi (Hospital Dongguk University of Gyeongju); Yun Seong Kim (Hospital Pusan National University of Yangsan); Jin Hwa Lee (Hospital Ewha Womans University Mokdong, Seoul); Myung-Goo Lee (Hospital Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon); Won-Yeon Lee (Hospital Yonsei University Wonju Christian, Wonju); Jin Young An (Hospital Chungbuk National University, Chenogiu); Gee Young Suh (Samsung Medical Center, Sungkyunkwan University, Seoul); Ki-Suck Jung (Hallym University Medical Center, Anyang)

Mexico: Coordinator: Asisclo J Villagómez Ortiz (Hospital Regional 1° de Octubre, ISSSTE, México DF)

César Cruz Lozano (Hospital Regional de Pemex, Ciudad Madero); Zalatiel Maycotte Luna (Hospital Ángeles de las Lomas, México DF); José Francisco López Baca (Hospital Regional de Zona No.1 del IMSS, México DF); José Elizalde (Instituto Nacional De Ciencias Médicas y Nutrición Salvador Zubirán, México DF); Guillermo Cueto Robledo (Hospital General de México, México DF); Mario Alonso Treviño Salinas (Hospital Universitario de Nuevo León ‘Dr. Eleuterio González’, Nuevo León); Ricardo Martinez Zubieta (Hospital Español de México, Miguel Hidalgo); Claudia Olvera-Guzman and Marco Montes De Oca (Centro Médico ABC, México DF), Silvio A. Ñamendys-Silva (Instituto Nacional de Cancerología, México DF); José Salvador Martínez Cano (Centenario Hospital Miguel Hidalgo, Aguascalientes); Jose Angel Baltazar Torres (Umae Hospital De Especialidades Dr. Antonio Fraga Mouret, México DF); Gustavo Morales Muñoz (Hospital Regional de Alta Especialidad de la Mujer, Villahermosa); Antonio Villa Delgado (Hospital Mérida Yucatán; Mérida); Javier Ladape Martinez (Hospital Juárez de México, Mexico DF).

Morocco: Coordinator: Amine Ali Zeggwagh (Hôpital Ibn Sina, Rabat)

Tarek Dendane (Hôpital Ibn Sina, Rabat); Abderrahim Azzouzi (Hôpital Ibn Sina, Rabat); Ahmed Sbihi (Hôpital Ibn Sina, Rabat); Wajdi Maazouzi and Mourad Amor (Hôpital des Specialites, Rabat); Charki Haimeur (Hôpital Militaire D’Instruction Mohamed V, Rabat).

Netherlands: Coordinator: Michael A. Kuiper (Medical Center Leeuwarden (MCL), Leeuwarden)

Matty Koopmans (Medical Center Leeuwarden (MCL), Leeuwarden); Uli Strauch, Dennis Bergmans, and Serge Heines (Universitair Medisch Centrum Maastricht, Maastricht); Sylvia den Boer (Spaarneziekenhuis, Hoofddorp); Bas M. Kors (Kennemer Gasthuis, Haarlem); Peter van der Voort (Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam); Paul J. Dennesen (Medisch Centrum Haaglanden, Den Haag); Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P.P.M. Gelissen, and Eduard Bootsma (Vrije Universiteit Medisch Centrum (VUMC), Amsterdam); Auke Reidinga (Tjongerschans Ziekenhuis, Heerenveen).

New Zealand: Coordinator: Jasmin Board and Andrew Davies (Alfred Hospital, Melbourne)

Kim Heus, Diane Mackle, and Paul Young (Wellington Hospital, Wellington); Rachael Parke, Eileen Gilder, and Jodi Brown (CVICU Auckland City Hospital, Auckland); Lynette Newby and Catherine Simmonds (DCCM Auckland City Hospital, Auckland); Jan Mehrtens and Seton Henderson (Christchurch Hospital, Christchurch); Tony Williams, Judi Tai, and Chantal Hogan (Middlemore, Auckland); Mary La Pine, John Durning, and Sheree Gare (Waikato, Hamilton); Troy Browne, Shirley Nelson, and Jennifer Goodson (Tauranga Hospital, Tauranga).

Panama: Julio Osorio (Hospital Rafael Hernández, Chiriquí)

Peru: Coordinator: Chabu Coronado

Rollin Roldán Mori (Hospital Edgardo Rebagliatti Martins, Lima); Rosa Luz López Martínez (Hospital Guillermo Almenara Irigoyen, Lima)

Poland: Adam Mikstacki and Barbara Tamowicz (Karol Marcinkowski University Of Medical Sciences, Poznan).

Portugal: Coordinator: Rui Moreno (Hospital de Santo Antonio dos Capuchos, Centro Hospitalar de Lisboa Central, E.P.E., Lisbon)

Eduardo Almeida (Hospital Garcia de Orta, Almada); Joana Silvestre (Centro Hospitalar de Lisboa Central); Heloisa Castro, Irene Aragão and Susana Alves Ferreira (Centro Hospitalar Do Porto – Hospital Geral De Santo António); Nelson Barros (Centro Hospitalar Trás-Os-Montes E Alto Douro, Vila-Real); Filomena Faria (Ipo); Carlos André Correia Casado (Hospital Da Luz); Fausto Fialho Moura (Hospital de Cascais); Paulo Marcal (Hospital De São Sebastião); Ricardo Matos (Hospital de Santo Antonio dos Capuchos, Centro Hospitalar de Lisboa Central, E.P.E., Lisbon); António Alvarez (Centro Hospitalar de Lisboa Norte)

Russian Federation: Coordinator: Edward Nicolayenko (Hospital No.1, Moscow)

Mikhail Kirov (Hospital No.1, Arkhangelsk); Andrey Yaroshetskiy (Hospital No.7, Moscow); Andrei Piontek (Hospital No.14, Ekaterinburg); Valery Subbotin (National Institute of Surgery Named After A.V. Vishnevskij, Moscow)

Saudi Arabia: Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E. Tabhan (King Saud Bin Abdulaziz University for Health Sciences, Riyadh)

Spain: Coordinator: Nicolas Nin

Alfonso Muñoz and César Aragón (Hospital Carlos Haya, Málaga); Ana Villagrá (Corporación Sanitaria y Universitaria Parc Taulí, Sabadell); Ainhoa Rosselló, and Joan Maria Raurich (Hospital Universitario Son Espasses, Mallorca); María Garitacelaya, Miguel Ángel González-Gallego, and Francisco Ortuño (Hospital Clínico Universitario San Carlos, Madrid); Miguel Fernández-Vivas (Hospital Virgen de la Arrixaca, Murcia); David Freire (Hospital Juan Canalejo, A Coruña); Francisco Guerrero and Francisco Manzano (Hospital Virgen de las Nieves, Granada); Juan Carlos Sotillo (Hospital Universitario Gregorio Marañón, Madrid); Alejandra Bustos (Hospital de Torrevieja); Alfredo Padrón, Pedro Rosas, Rafael Morales, and Liliana Caipe (Hospital Doctor Negrín, Las Palmas de Gran Canaria); Maurizio Bottiroli (Hospital de la Santa Creu i Sant Pau, Barcelona); José María Nicolás (Hospital Clinic-IDIBAPS, Barcelona); Marta Ugalde (Hospital de Cruces, Barakaldo); Javier Ruiz (Hospital Sagrado Corazón, Barcelona); Lucia Capilla (Hospital Morales Meseguer, Murcia); Guillermo Muñiz (Hospital Central de Asturias, Oviedo); Jesús Sánchez-Ruiz (Hospital General de Jerez de la Frontera); Javier Cebrián, Begoña Balerdi, Elena Parreño, and Alvaro van Bommel (Hospital Universitario La Fe, Valencia); César Pérez-Calvo (Fundación Jiménez Díaz, Madrid); Irene Dot (Hospital del Mar, Barcelona); Javier Blanco (Complejo Hospitalario de Ciudad Real); Raquel Manzanedo and José J. Blanco (Hospital Insular de Gran Canaria); Daniel Fontaneda, Raúl González, and Javier Díaz Domínguez (Complejo Hospitalario de León); Alfonso Moreno (Hospital San Pedro. Logroño); Antonio Reyes and Ian Carrasco (Hospital de la Princesa, Madrid); Itziar Mintegui, Rosa Sebastián, and Javier García-Alonso (Complejo Hospitalario de Donostia); Carolina Lorencio and Josep Maria Sirvent (Hospital Universitario Dr.Josep Trueta, Girona); Patricia Jimeno (Hospital General de Segovia); Miguel León (Hospital Arnau de Vilanova, Lleida); Pedro Galdos (Hospital Universitario Puerta de Hierro, Majadahonda); Nuria Alonso (Hospital Universitario Nuestra Santa María del Rosell, Cartagena); Julia López-Díaz (Hospital Universitario La Paz, Madrid); María Victoria de la Torre, Jorge Vidal Hernández, and Nicolás Zamboschi (Hospital Universitario Virgen de la Victoria, Málaga); Francisco Lucena (Hospital Universitario de Valme, Sevilla); Gemma Rialp (Hospital Son Llatzer, Mallorca); Raquel Montoiro (Hospital Clínico Lozano Blesa, Zaragoza); Victoria Goñi, María Ángeles Pena, and Antonio Maestre (Hospital Virgen del Rocío, Sevilla); Marc Fabra, Jacinto Baena, and Eva Benveniste (Hospital Germans Trias I Pujol, Badalona); Susana Temprano (Hospital 12 de Octubre, Madrid); Jesús Sánchez (Hospital de Rio Hortega, Valladolid); Carmen Campos (Hospital Universitario Dr.Peset, Valencia); Sara Cabañes (Hospital Santiago Apóstol, Vitoria); María Elena Pérez-Losada and José Claudio Leo (Complejo Hospitalario de Salamanca); Enrique Piacentini (Hospital Mutua de Terrassa); María del Carmen de la Torre (Hospital de Mataró); Laura Álvarez-Montero, Fernando Sánchez (Hospital Xeral Calde, Lugo); Antonio Viñuales (Hospital Lluis Alcanyis, Xàtiva); Bernabé Álvarez (Hospital General de Alicante); Javier Castañeda (Hospital Clínico de Valladolid); Ángela Alonso (Hospital de Fuenlabrada); María Isabel Ruiz (Complejo Hospitalario de Jaén); Pedro Jesús Domínguez (Hospital Juan Ramón Jiménez, Huelva); Marcos Delgado (Complejo Hospitalari de Manresa); Eugenio Palazón (Hospital Universitario Reina Sofía, Murcia); Antonio García-Jiménez (Hospital Arquitecto Marcide, Ferrol); Rosa Álvaro (Hospital de La Plana, Castellón); Clara Laplaza, Eva Regidor, and Enrique Maraví (Complejo Hospitalario de Navarra, Pamplona); José María Quiroga (Hospital de Cabueñes, Gijón); Amalia Martínez de la Gandara (Hospital Infanta Leonor, Madrid); Cecilia Carbayo (Hospital Torrecárdenas, Almería); María Luisa Navarrete (Hospital San Juan, Alicante); Manuel Valledor and Raquel Yano (Hospital San Agustín, Avilés); José María Gutiérrez (Hospital General de Albacete); Javier González-Robledo (Hospital Clínico de Salamanca); Amparo Ferrandiz, Alberto Belenguer, and Lidón Mateu (Hospital General de Castellón); Laura Sayagues (Complejo Hospitalario de Santiago de Compostela); María José Tolón (Hospital Royo Vilanova, Zaragoza); Nieves Franco (Hospital de Móstoles); Elena Gallego (Hospital San Pedro de Alcántara, Cáceres); Félix Lacoma (Hospital Quirón, Madrid); Patricia Albert (Hospital del Sureste, Arganda); Vicente Arraez (Hospital Universitario General, Elche); Mar Gobernado (Hospital General de Soria); Susana Moradillo (Hospital Río Carrión, Palencia); Carolina Gímenez-Esparza (Hospital de la Vega Baja, Orihuela); Teresa Sánchez de Dios (Complejo Hospitalario Montecelo, Pontevedra); Carlos Marian Crespo (Hospital General de Guadalajara); Cecilia Hermosa, Federico Gordo (Hospital del Henares, Coslada); Genis Carrasco (Hospital SCIAS, Barcelona); María Ángeles Alonso (Trauma ICU, Hospital 12 de Octubre, Madrid); Alejandro Algora (Fundación Hospital Universitario de Alcorcón, Madrid); Raúl de Pablo (Hospital Príncipe de Asturias, Alcalá de Henares); Sofía García (Hospital del Poniente, El Ejido); Ana Carolina Caballero (Hospital de Zamora); José María Montón (Hospital Obispo Polanco, Teruel); Teresa Mut (Hospital Provincial de Castellón); Eva Manteiga (Hospital Infanta Cristina, Parla); Alejandro de la Serna (Hospital de Galdakao); Ana Esther Trujillo (Hospital General de La Palma); Rafael Blancas (Hospital del Tajo, Aranjuez); Inmaculada Vallverdú (Hospital Universitario San Juan, Reus); José Manuel Serrano (Hospital Universitario Reina Sofía, Córdoba); Miquel Ferrer (Hospital Clinic-IDIBAPS, Barcelona); Juan Diego Jiménez (Hospital de Don Benito); Carlos Gallego (Hospital Infanta Elena, Valdemoro); Dolores Vila (Hospital Meixoeiro, Vigo); Luis Marina (Complejo Hospitalario de Toledo); Valentín Parra (Hospital de Sagunto); Juan Ramón Cortés (Complejo Hospitalario de Ourense).

Taiwan: Chen Chin-Ming and Ai-Chin Cheng (Chi Mei Medical Center, Tainan City)

Tunisia: Coordinator: Fekri Abroug (Hospital Fattouma Bourguina, Monastir)

Besbes Mohamed (Hospital Abderrahmane Mami, Ariana); Imed Chouchene (Hospital Universitarie Farhat Hached, Sousse); Mounir Bouaziz (CHU Habib Bourguiba, Sfax); Stambouli Neji and Islem Ouanes (Hospital Fattouma Bourguina, Monastir); Ayed Samia (Hospital Taher Sfar City, Mahdia).

Turkey: Coordinator: Nahit Cakar (Istanbul Medical Faculty, Istanbul)

Ismail Kati (Medical Faculty of Yuzuncu Yil University, Van); Ali Aydım Altunkan (Faculty of Medicine, Mersin University); Remzi Iscimen (Uludag University Faculty of Medicine, Bursa); Zafer Dogan (Sutcu İmam University, Kahramanmaras); Bilge Çetin (Erciye Üniversity); Tayfun Adanir (Atatürk Hospital, Izmir); Sabriye Guvenc (Anadolu Medical Center Istanbul); Unase Büyükkoçak (Kirikkale University).

USA: Coordinator: Antonio Anzueto (University Hospital San Antonio and South Texas Veterans Health Care System)

Ashley Ellis and Gary Kinasewitz (Oklahoma University Health Science Center and VA Medical Center, Oklahoma City); Allan Walkey and Phil Alkana (Boston Medical Center, Boston); Gregory A. Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, and Larry Welder (University of Iowa Hospitals and Clinics, Iowa City); Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, and Christopher Spradley (Temple Clinic, Scott and White Healthcare, Temple); Dimple Tejwani, Sindhaghatta Venkatram, and Gilda Diaz-Fuentes (Bronx Lebanon Hospital Center, New York); Amber Monson, Anthony Saleh, Madhav Gudi, and George Liziamma (New York Methodist Hospital, New York); Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, and Crissie Despirito (University of Louisville School of Medicine Hospital, Louisville); Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, and Steven Y. Chang (UMDNJ-New Jersey Medical School, Newark); Brian Sherman, Rosanna Del Giudice, and John Oropell (The Mount Sinai Medical Center, New York); Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, and Matthew Kirchner (Vanderbilt University School Of Medicine, Nashville); Ashley Ellis and Gary Kinasewitz (Oklahoma City VA Medical Center, Oklahoma City); Erwin J. Oei, Sebastian Circo, Nelson Medina, and Mohammed Al-Jagbeer (Morristown Medical Center, Morristown); V.J. Cardenas, Jr and Smyth Smith (University Of Texas Medical Branch at Galveston); Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, and Travis Parry (University Hospital San Antonio and South Texas Veterans Health Care System); Craig A. Piquette and Kerry Canady (Omaha VA Medical Center. Omaha); Rahul Nanchal and Dana K. Soetaert (Medical College of Wisconsin); Maria del Mar Torres-Perez, Carlos Robles-Arias, and William Rodriguez-Cintron (VA Caribbean Health Care System, San Juan, Puerto Rico); Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, and Erin Braden (Baystate Medical Center, Springfield); Geneva Tatem (Henry Ford Hospital Detroit)

Uruguay: Coordinator: Javier Hurtado (Hospital Español and CUDAM, Montevideo)

Alberto Deicas (CASMU Nº2, Montevideo); Daniel Weiss (Hospital Pasteur, Montevideo); Marta Beron (Hospital Maciel, Montevideo); Román Garrido (Hospital Evangélico, Montevideo); Cristina Santos and Mario Cancela (Hospital de Clínicas, Montevideo); Raúl Lombardi (Impasa, Montevideo); Pedro Alzugaray (CAAMOC, Carmelo, Sanatorio Americano, Montevideo and Orameco, Colonia); Jorge Gerez (Hospital Policial, Montevideo); Silvia Mareque (Sanatorio CAMS, Mercedes); Graciela Franca (Circulo Católico, Montevideo); Oscar Cluzet (Sanatorio Americano, Montevideo); Edgardo Nuñez (Sanatorio Mautone and Hospital de Maldonado, Maldonado); Julio Pontet (Hospital de Florida, Florida); Sergio Cáceres (Centro Cardiológico Sanatorio Americano, Montevideo); Elias Caragna (CRAMI, Las Piedras); Alberto Soler (COMEPA and Hospital Escuela del Litoral, Paysandú); Frank Torres (Sanatorio Cantegril, Punta del Este); Gastón Pittini (CAAMEPA, Pando).

Venezuela: Coordinator: Gabriel d`Empaire (Hospital de Clínicas de Caracas)

Stevens Salva and Fernando Pérez (Hospital de Clínicas de Caracas); Clara Pacheco and Zoraida Parra (Hospital Clínico Universitario de Caracas); Ingrid Von der Osten (Hospital Miguel Pérez Carreño, Caracas); Luis Williams and José Salinas (Hospital Centro de Especialidades de Anzoategui).

Vietnam: Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, and Nghuyen ba Tuan (Viet Duc Hospital, Hanoi).

Contributorship: Study concept and design: Alejandro C. Arroliga, Fernando Frutos-Vivar, Alfonso Muriel, Oscar Peñuelas; Coordination of data acquisition: Nicolás Nin, Andrew R. Davies, Pravin Amin, Bin Du, Konstantinos Raymondos, Arnaud W. Thille, Laurent Brochard, Fernando Rios, Damian A. Violi, Salvatore M. Maggiore, Marco Antonio Soares, Marco González, Fekri Abroug, Hans-Henrik Bülow, Javier Hurtado, Michael A. Kuiper, Rui P.Moreno, Amine Ali Zeggwagh, Asisclo J. Villagómez, Manuel Jibaja, Luis Soto, Gabriel D’Empaire, Dimitrios Matamis, Younsuck Koh, Antonio Anzueto, Niall D. Ferguson; Statistical analysis: Alfonso Muriel, Victor Abraira; Drafting of manuscript: Alfonso Muriel, Oscar Peñuelas, Fernando Frutos-Vivar; Critical revision of manuscript: Alejandro Arroliga, Victor Abraira, Nicolás Nin, Andrew R. Davies, Pravin Amin, Bin Du, Konstantinos Raymondos, Arnaud W. Thille, Laurent Brochard, Fernando Rios, Damian A. Violi, Salvatore M. Maggiore, Marco Antonio Soares, Marco González, Fekri Abroug, Hans-Henrik Bülow, Javier Hurtado, Michael A. Kuiper, Rui P.Moreno, Amine Ali Zeggwagh, Asisclo J. Villagómez, Manuel Jibaja, Luis Soto, Gabriel D’Empaire, Dimitrios Matamis, Younsuck Koh, Antonio Anzueto, Niall D. Ferguson.