Preoperative intra-aortic balloon pump inserted in acute myocardial infarction patients without cardiogenic shock undergoing surgical coronary revascularization.

OBJECTIVES: The benefit of preoperative intra-aortic balloon pump implantation in high-risk cardiac surgery patients is still debated. The role of preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting remains unknown. This study aimed to determine the efficacy and safety of the preoperative intra-aortic balloon pump insertion in those patients undergoing off-pump coronary artery bypass grafting. METHODS: A total of 421 consecutive acute myocardial infarction patients without cardiogenic shock who underwent isolated off-pump coronary artery bypass grafting were enrolled in this retrospective observational propensity score-matched analysis study. Patients who received intra-aortic balloon pump before off-pump coronary artery bypass grafting (the intra-aortic balloon pump group, n = 157) were compared with those who had not (control group, n = 264). The 30-day postoperative survival, postoperative complications, and postoperative hospital length of stay were compared between the two groups. RESULTS: A total of 99 pairs of patients were matched. The preoperative intra-aortic balloon pump did not show a 30-day postoperative survival benefit compared with the control group (hazard ratio, 0.9; 95% confidence interval, 0.2-4.2; p = 0.92). Patients with preoperative intra-aortic balloon pump were more likely to have shorter postoperative lengths of stay (8 (6-11) days vs. 10 (6-15) days, p = 0.02) and decreased total days in the hospital (median days: 18.2 vs. 21.8, p = 0.02) compared to patients without balloon pumps. CONCLUSION: Preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting improved convalescence as shown by significantly shorter postoperative lengths of hospital stay.

The effect of methylprednisolone prophylaxis on inflammatory monocyte subsets and suppressive regulatory T cells of patients undergoing cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) during open-heart surgery triggers an inflammatory response that can cause significant morbidity and mortality. Human monocytes and regulatory T (Treg) cells are phenotypically and functionally heterogeneous and have been shown to play a significant role in the inflammatory dysfunction triggered by CPB. Glucocorticoids (GCs) have been widely administered for decades in patients undergoing CPB to reduce this inflammatory response. However, it has not been clearly established how routine prophylactic administration of glucocorticoids (GCs) affects monocyte and Treg subsets. METHODS: Thirty-six patient who underwent heart surgery with CPB were randomly assigned to a methylprednisolone group (MG, N = 18; 500 mg in the CPB priming) and a non-methylprednisolone group (NMG, N = 18). The circulating monocyte and Treg subsets were analyzed by flow cytometry. RESULTS: The MG and NMG groups had comparable percentages of monocyte subsets and similar expression levels of HLA-DR, CD86, CD64 and toll-like receptor 4 (TLR4). Remarkably, methylprednisolone increased the percentage of CD4+CD25+ Treg cells among CD4+ T cells in patients undergoing CPB, but did not increase the proportion of suppressive Treg cells, either resting or activated, in these patients undergoing CPB. CONCLUSIONS: Our results showed that prophylactic administration of methylprednisolone neither decreased the percentages and counts of inflammatory monocyte subsets nor did it induce the expansion of suppressive Treg cells in patients undergoing CPB. These results clarified the effects of GCs on cell-mediated immune responses and provided additional evidence in practice. TRIAL REGISTRATION: Clinicaltrials.gov : NCT01296074. Registered 14 February 2011.

Immature monocytes contribute to cardiopulmonary bypass-induced acute lung injury by generating inflammatory descendants.

BACKGROUND: As immune regulatory and effector cells, monocytes play an important role in the blood-extracorporeal circuit contact-related acute lung injury in patients undergoing cardiopulmonary bypass (CPB). However, circulating monocytes are phenotypically and functionally heterogeneous, so we characterised how immature monocytes affect acute lung injury induced by CPB. METHODS: The identification and dynamic changes in monocyte subsets were monitored by flow cytometry in patients undergoing CPB and in a rat model of CPB. The differentiation and migration of monocyte subsets were explored by in vitro cultures and adoptive transfer in the CPB rat model. RESULTS: We observed a dramatic increase of two monocyte subsets in the peripheral blood of patients undergoing CPB, involving tumour necrosis factor (TNF)-α-producing, mature intermediate CD14highCD16+ monocytes and a novel immature CD14lowCD16- subset. The immature CD14lowCD16- monocytes possessed limited ability for TNF-α production, and failed to suppress T-cell proliferation mediated by T-cell receptor signalling. However, these immature cells were highly proliferative and could differentiate into TNF-α producing, mature CD14highCD16+ monocytes. In the rat model of CPB, we further demonstrated that CPB induced migration of immature monocytes into the lungs, either from the bone marrow or from the spleen. Moreover, we confirmed the hypothesis that immature subsets could contribute to CPB-induced acute lung injury by giving rise to TNF-α producing descendants. CONCLUSIONS: The immature CD14lowCD16- monocytes might contribute to blood-circuit contact-induced acute lung injury by generating TNF-α-producing, mature monocytes. New strategies based on monocyte manipulation could be a promising therapeutic approach for minimising CPB-related lung injury.

Superior vena cava drainage improves upper body oxygenation during veno-arterial extracorporeal membrane oxygenation in sheep.

INTRODUCTION: Differential hypoxia is a pivotal problem in patients with femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) support. Despite recognition of differential hypoxia and attempts to deliver more oxygenated blood to the upper body, the mechanism of differential hypoxia as well as prevention strategies have not been well investigated. METHODS: We used a sheep model of acute respiratory failure that was supported with femoral VA ECMO from the inferior vena cava to the femoral artery (IVC-FA), ECMO from the superior vena cava to the FA (SVC-FA), ECMO from the IVC to the carotid artery (IVC-CA) and ECMO with an additional return cannula to the internal jugular vein based on the femoral VA ECMO (FA-IJV). Angiography and blood gas analyses were performed. RESULTS: With IVC-FA, blood oxygen saturation (SO2) of the IVC (83.6 ± 0.8%) was higher than that of the SVC (40.3 ± 1.0%). Oxygen-rich blood was drained back to the ECMO circuit and poorly oxygenated blood in the SVC entered the right atrium (RA). SVC-FA achieved oxygen-rich blood return from the IVC to the RA without shifting the arterial cannulation. Subsequently, SO2 of the SVC and the pulmonary artery increased (70.4 ± 1.0% and 73.4 ± 1.1%, respectively). Compared with IVC-FA, a lesser difference in venous oxygen return and attenuated differential hypoxia were observed with IVC-CA and FA-IJV. CONCLUSIONS: Differential venous oxygen return is a key factor in the etiology of differential hypoxia in VA ECMO. With knowledge of this mechanism, we can apply better cannula configurations in clinical practice.

Intra-aortic balloon pump impacts the regional haemodynamics of patients with cardiogenic shock treated with femoro-femoral veno-arterial extracorporeal membrane oxygenation.

AIMS: To investigate the impact of intra-aortic balloon pump (IABP) on the regional haemodynamics of patients with severe cardiogenic shock undergoing femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS AND RESULTS: From July 2017 to April 2018, a total of 39 adult patients with cardiogenic shock receiving both IABP and ECMO for circulatory support were enrolled consecutively in a university-affiliated cardiac surgery intensive care unit. The blood flow rates (BFRs) of the bilateral femoral artery (IABP side: iFA, ECMO side: eFA) and carotid artery (left: LCA, right: RCA) and the velocity time integral (VTI) of aortic root were assessed by ultrasonography and compared when IABP was on and off. Seventeen of 39 (43.6%) patients survived to discharge, and 29 (74.4%) survived on ECMO. A total of 172 pairs of data (IABP on and off) were collected in this study, measured on the median of 2.0 (1.0, 4.5) days after patients received VA-ECMO. The BFR on both sides of FA (iFA: 176.4 ± 104.5 vs. 152.2 ± 139.8 mL/min, P < 0.01; eFA: 299.3 ± 279.9 vs. 242.4 ± 258.8 mL/min, P < 0.01) and the aortic VTI (10.1 ± 4.4 vs. 8.5 ± 4.4 cm, P < 0.01) decreased significantly when turning the IABP off, while the BFR on both sides of CA remained unchanged (LCA: 555.7 ± 326.9 vs. 578.6 ± 328.0 mL/min, P = 0.27; RCA: 550.0 ± 331.1 vs. 533.0 ± 303.5 mL/min, P = 0.30). The LCA BFR dramatically increased after turning the IABP off (296.8 ± 129.7 vs. 401.4 ± 278.1 mL/min, P = 0.02) in patients with cardiac stunning (defined as pulse pressure ≤ 5 mmHg). However, there was no significant difference in LCA BFR between IABP-On and IABD-Off (359.6 ± 105.4 mL/min vs. 389.6 ± 139.3 mL/min, P = 0.31) in patients with cardiac stunning receiving a higher ECMO blood flow (> 3.5 L/min). CONCLUSIONS: Concomitant IABP used in patients undergoing femoro-femoral VA-ECMO was associated with increased aortic VTI and BFR in bilateral FA. The change in CA BFR depended on cardiac function. A decreased LCA BFR was observed in patients with cardiac stunning when IABP was turned on, which might be compensated by a higher ECMO blood flow. Further study is needed to confirm the relationship between BFR and extremities and neurological complications.

Drainage From Superior Vena Cava Improves Upper Body Oxygenation in Patients on Femoral Veno-Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: To investigate the feasibility of drainage from the superior vena cava (SVC) to improve upper body oxygenation in patients with cardiogenic shock undergoing femoral veno-arterial extracorporeal membrane oxygenation (VA ECMO). METHODS: Seventeen adult patients receiving peripheral femoral VA ECMO for circulatory support were enrolled. The femoral drainage cannula was shifted three times (from the inferior vena cava (IVC) level to the SVC level and then the IVC level again), all under ultrasound guidance, at an interval of 15 minutes. The blood gas levels of the right radial artery (RA) and SVC and cerebral oxygen saturation (ScO2) were measured and compared. RESULTS: Fifteen patients (88.2%) were successfully weaned from ECMO, and 12 patients (70.6%) survived to discharge. The oxygen saturation (SO2) and oxygen partial pressure (PO2) of the RA (97.0 ± 3.5% to 98.3 ± 1.5%, P < 0.05, SO2; 127.4 ± 58.2 mmHg to 153.1 ± 67.8 mmHg, P < 0.05, PO2) and SVC (69.5 ± 9.0% to 75.7 ± 8.5%, P < 0.05, SO2; 38.5 ± 5.6 mmHg to 43.6 ± 6.4 mmHg, P < 0.05, PO2) were increased; ScO2 was also increased on both sides (left: 50.6 ± 8.6% to 55.0 ± 9.0%, P < 0.05; right: 48.7 ± 9.2% to 52.3 ± 9.8%, P < 0.05) when the femoral drainage cannula was shifted from the IVC level to the SVC level. When the femoral drainage cannula was shifted from SVC level to the IVC level again, the SO2 and PO2 of RA (98.3 ± 1.5% to 96.9 ± 3.2%, P <0.05, SO2; 153.1 ± 67.8 mmHg to 125.8 ± 63.3 mmHg, P <0.05, PO2) and SVC (75.7 ± 38.5% to 70.4 ± 7.6%, P <0.05, SO2; 43.6 ± 6.4 mmHg to 38.9 ± 4.5 mmHg, P <0.05, PO2) were decreased; ScO2 was also reduced on both sides (left: 55.0 ± 9.0% to 50.7 ± 8.2%, P < 0.05; right: 52.3 ± 9.8% to 48.7 ± 9.3%, P <0.05). CONCLUSION: Drainage from the SVC by shifting the cannula upward could improve upper body oxygenation in patients with cardiogenic shock undergoing femoral VA ECMO. This cannulation strategy provides an alternative solution for differential hypoxia.

Effect of increasing mean arterial blood pressure on microcirculation in patients with cardiogenic shock supported by extracorporeal membrane oxygenation.

BACKGROUND: Little is known about the effect of mean arterial blood pressure (MAP) augmentation on the microcirculation in cardiogenic-shock patients with peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support. We investigated the effect of increasing MAP on the microcirculation in cardiogenic-shock patients with ECMO support. METHODS: A single-center prospective observational study under taken in ICU patients undergoing ECMO support for post-cardiotomy cardiogenic shock was carried out. Patients with MAP <60 mmHg treated with ECMO support were the study cohort. Inotropic and vasopressor agents (dopamine, dobutamine, norepinephrine or epinephrine) were administered to maintain the MAP at 60-90 mmHg. Hemodynamic and microcirculatory data were obtained at a baseline MAP of <60 mmHg and 1 h after target MAP was reached. As parameters of microcirculation, we measured thenar eminence tissue oxygenation (StO2) and its change during the vessel obstruction test and cerebral tissue oxygenation (rSO2) with near-infrared spectroscopy. RESULTS: Seventeen patients were enrolled in the study. MAP of all patients increased and reached predefined therapeutic targets (52 [50-54.5] vs.74 [70-78.5] mmHg; p < 0.001). To obtain these targets, doses of inotropic agents were increased (inotrope score increased from 14 [15.5-28] µg/kg/min; p < 0.001). No obvious changes were observed in thenarmuscleStO2 and cerebral rSO2. Thenar muscle StO2 desaturation slope and resaturation slopes during the vessel obstruction test were also unchanged. CONCLUSIONS: Increasing MAP from <60 mmHg to 60-90 mmHg did not affect microcirculation variables in cardiogenic-shock patients with ECMO support.

Vascular complications in adult postcardiotomy cardiogenic shock patients receiving venoarterial extracorporeal membrane oxygenation.

BACKGROUND: The rate, prognostic impacts, and predisposing factors of major vascular complications (MVCs) in patients underwent venoarterial extracorporeal membrane oxygenation (VA-ECMO) by surgical cut-down are poorly understood. The purpose of this study was to identify these parameters in adult VA-ECMO patients. METHODS: Adult postcardiotomy cardiogenic shock (PCS) patients receiving VA-ECMO by femoral surgical cut-down cannulation from January 2004 to December 2015 were enrolled in this study. Patients were separated into two groups depending on the presence of MVCs. Multivariate logistic regression was performed to identify factors independently associated with MVCs. RESULTS: Of 432 patients with PCS treated with VA-ECMO, 252 patients (58.3%) were weaned off VA-ECMO and 153 patients (35.4%) survived to discharge. MVCs were seen in 72 patients (16.7%), including bleeding or hematoma in the cannulation site (8.6%), limb ischemia requiring fasciotomy (8.6%), femoral artery embolism (0.7%), and retroperitoneal bleeding (0.7%). The rate of survival to discharge was 16.7 and 39.2% in patients with or without MVCs, respectively (p < 0.001). Obesity, concomitant with intra-aortic balloon pump (IABP), Sequential Organ Failure Assessment (SOFA) score at 24 h post-ECMO, and hemostasis disorder were shown to be associated with MVCs. MVCs were an independent risk factor for in-hospital mortality by multivariate analysis (odds ratio 3.91; 95% confidence interval, 1.67-9.14; p = 0.013). CONCLUSIONS: MVCs are common and associated with higher in-hospital mortality among adult PCS patients receiving peripheral VA-ECMO support. The obesity, concomitant with IABP, SOFA score at 24 h post-ECMO, and hemostasis disorder were independent risk factor of MVCs.

Urinary trypsin inhibitor attenuated inflammatory response of patients undergoing cardiopulmonary bypass by inducing activated Treg cells.

The urinary trypsin inhibitor (ulinastatin) is used in the clinic to prevent inflammatory responses in patients undergoing cardiopulmonary bypass (CPB); however, the anti-inflammatory mechanism is unclear. In the current study, we recruited 40 patients undergoing selective cardiac valve replacement surgery; and these patients were randomly divided into two groups (ulinastatin group [UG] and control group [CG]). We collected peripheral blood preoperatively, at the end of CPB, and postoperative days 1 and 3 and analyzed the kinetic changes in regulatory T (Treg) cell subsets. There was no statistically significant difference in the number of CD4(+) T cells between the two groups. The number of CD4(+)CD25(+) Treg cells, especially the suppressive activated Treg (aTreg) subset, was higher in the UG than the CG 1 and 3 days postoperatively. Thus, ulinastatin alleviated the inflammatory response during CPB by inducing the expansion of aTreg cells.