Off-pump versus on-pump coronary artery bypass grafting in frail patients: study protocol for the fragile multicenter randomized controlled trial

Abstract Introduction: Advances in modern medicine have led to people living longer and healthier lives. Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. When it comes to CABG surgery, randomized controlled clinical trials have primarily focused on low-risk (ROOBY, CORONARY), elevated-risk (GOPCABE) or high-risk patients (BBS), but not on frail patients. Therefore, we believe that off-pump CABG could be an important technique in patients with limited functional capacity to respond to surgical stress. In this study, the authors introduce the new national, multicenter, randomized, controlled trial "FRAGILE", to be developed in the main cardiac surgery centers of Brazil, to clarify the potential benefit of off-pump CABG in frail patients. Methods: FRAGILE is a two-arm, parallel-group, multicentre, individually randomized (1:1) controlled trial which will enroll 630 patients with blinded outcome assessment (at 30 days, 6 months, 1 year, 2 years and 3 years), which aims to compare adverse cardiac and cerebrovascular events after off-pump versus on-pump CABG in pre-frail and frail patients. Primary outcomes will be all-cause mortality, acute myocardial infarction, cardiac arrest with successful resuscitation, low cardiac output syndrome/cardiogenic shock, stroke, and coronary reintervention. Secondary outcomes will be major adverse cardiac and cerebrovascular events, operative time, mechanical ventilation time, hyperdynamic shock, new onset of atrial fibrillation, renal replacement therapy, reoperation for bleeding, pneumonia, length of stay in intensive care unit, length of stay in hospital, number of units of blood transfused, graft patency, rate of complete revascularization, neurobehavioral outcomes after cardiac surgery, quality of life after cardiac surgery and costs. Discussion: FRAGILE trial will determine whether off-pump CABG is superior to conventional on-pump CABG in the surgical treatment of pre-frail and frail patients. Trial registration: ClinicalTrials.gov, ID: NCT02338947. Registered on August 29th 2014; last updated on March 21st 2016.

Skeletonized internal thoracic artery is associated with lower rates of mediastinitis in elderly undergoing coronary artery bypass grafting surgery / Artéria torácica interna esqueletizada está associada a menores taxas de mediastinite em idosos submetidos à cirurgia de revascularização miocárdica

BACKGROUND AND OBJECTIVES: Mediastinitis is a serious complication of median sternotomy and is associated to significant morbidity and mortality. The aim of this study is to identify which option of harvesting internal thoracic artery (ITA), pedicled or skeletonized, is associated with lower rates of mediastinitis after coronary artery bypass grafting surgery (CABG) in elderly, in the Division of Cardiovascular Surgery of PROCAPE. METHODS: Retrospective study of 160 elderly who underwent consecutive CABG between May 2007 and June 2011. Eleven preoperative variables, four intraoperative variables and eight postoperative variables possibly involved in the development of postoperative mediastinitis were evaluated between two groups: CABG with skeletonized ITA (n=80) and pedicled ITA (n=80). Univariate and multivariate logistic regression analyses were applied. RESULTS: The incidence of mediastinitis was 6.8 percent (n=11), with a lethality rate of 54.5 percent (n=6). The skeletonized ITA group were more exposed than pedicled ITA group to obesity (n=12 vs. n=4; 15 percent vs. 5 percent; P=0.035) and multiple transfusions (n=25 vs. n=11; 31.2 percent vs. 13.7 percent; P=0.008). The pedicled ITA group presented a greater risk of mediastinitis after CABG than skeletonized ITA group (n=10 vs. n=1; 12.5 percent vs. 1.2 percent; Unadjusted OR 11.3; 95 percent CI 1.4 - 241.5; P=0.008). In multivariate analysis, this difference maintained statistically significant (Adjusted OR 5.2; 95 percent CI 1.5-495.8; P=0.012), being considered an independent association. CONCLUSIONS: We suggest that elderly should be considered for strategies to minimize risk of infection. In elderly that undergo unilateral ITA, the problem seems to be related to how ITA is harvested. Elderly should always be considered for use of skeletonized ITA.

JUSTIFICATIVA E OBJETIVOS: Mediastinite é séria complicação da esternotomia mediana e está associada a significativa morbidade e mortalidade. O objetivo deste estudo é identificar qual técnica de obtenção da artéria torácica interna (ATI), dissecção pediculada ou esqueletizada, está associada a menores taxas de mediastinite após cirurgia de revascularização miocárdica (CRM) em idosos, na Divisão de Cirurgia Cardiovascular do PROCAPE. MÉTODOS: Estudo retrospectivo de 160 idosos submetidos consecutivamente à CRM entre maio/2007 e junho/2011. Onze variáveis pré-operatórias, quatro intraoperatórias e oito pós-operatórias, possivelmente envolvidas no desenvolvimento de mediastinite após CRM, foram avaliadas entre dois grupos: CRM com ATI esqueletizada (n=80) e ATI pediculada (n=80). Análises univariada e multivariada por regressão logística foram aplicadas. RESULTADOS: A incidência de mediastinite foi 6,8 por cento (n=11), com taxa de letalidade de 54,5 por cento (n=6). Grupo ATI esqueletizada foi mais exposto à obesidade (n=12 vs. n=4; 15 por cento vs. 5 por cento, P=0,035) e múltiplas transfusões (n=25 vs. n=11; 31,2 por cento vs. 13,7 por cento; P=0,008) do que grupo ATI pediculada. Grupo ATI pediculada apresentou maior risco de mediastinite após CRM que grupo ATI esqueletizada (n=10 vs. n=1; 12,5 por cento vs. 1,2 por cento; OR não-ajustado 11,3; IC 95 por cento 1,4-241,5; P=0,008). Na análise multivariada, esta diferença manteve-se estatisticamente significativa (OR ajustado 5,2; IC 95 por cento 1,5-495,8; P=0,012), sendo considerada uma associação independente. CONCLUSÕES: Sugerimos que os idosos devem ser considerados para estratégias de minimização de risco de infecção. Em idosos submetidos à CRM com ATI unilateral, o problema parece estar relacionado à forma como a ATI é obtida. Idosos devem ser sempre considerados para o uso de ATI esqueletizada.