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Low-weight (<10 kg) children undergoing cardiac surgery with cardiopulmonary bypass are prone to dilution and consumption of soluble coagulation factors and fibrinogen. Low levels of fibrinogen may represent a possible cause of severe postoperative chest drain blood loss. The present study investigates the association between post–cardiopulmonary bypass fibrinogen levels and postoperative chest drain blood loss and severe bleeding, aiming to identify possible cut-off values to trigger specific interventions.
Prospective cohort study on 77 patients weighing <10 kg undergoing cardiac surgery with cardiopulmonary bypass. Haemostasis and coagulation data were collected before surgery (standard tests and thromboelastometry), after protamine (thromboelastometry) and at the arrival in the intensive care unit (standard tests). The primary outcome variable was severe bleeding (chest drain blood loss >30 ml kg-1/24h).
Factors being independently associated with severe bleeding were the international normalized ratio and the fibrinogen levels at the arrival in the intensive care unit. Once corrected for other confounders, fibrinogen levels had an odds ratio of 0.2 (95% confidence interval = 0.011-0.54) per 1 gL-1 for severe bleeding. The discrimination power was fair (area under the curve = 0.770). The best cut-off value was identified at a fibrinogen level of 150 mg dL-1, with a sensitivity of 52%, a specificity of 85% and a positive predictive value of 60% for severe bleeding.
Both a prolonged international normalized ratio and low fibrinogen levels were predictive for severe bleeding, underscoring the role of coagulation factors dilution and consumption in this specific patient population.

A high perioperative blood lactate level has been reported to be associated with poor outcomes after cardiac surgery. More than isolated peaks of lactate values, it should be more interesting to take into account changes in intraoperative blood lactate level (∆Lact). This large-scale retrospective study evaluated the relationship between ∆Lact and overall intensive care unit morbidity and 30-day all-cause mortality.
Perioperative data from consecutive patients undergoing on-pump cardiac surgery between September 2010 and June 2016 were retrospectively analysed through our institutional database including clinical, transfusion and laboratory test results implemented prospectively by physicians. Blood lactate levels were initially measured after induction of anaesthesia (baseline) and periodically during the surgery. The ∆Lact was defined as the difference between the highest intraoperative blood lactate and the baseline lactate level and offered the opportunity to stratify patients into four subgroups: ⩽0, 0.1-0.9, 1-1.9 and ⩾2 mmol L−1.
From the 7,795 patients found eligible during the study period, 7,447 patients were analysed. The median ∆Lact of our patients was 0.6 (0.3-1) mmol L−1. Most of the studied patients (65.9%) exhibited a ∆Lact between 0.1 and 0.9 mmol L−1. A concentration-dependent relationship was observed between ∆Lact and intensive care unit morbidity and 30-day mortality. After adjustment for co-variables, all ∆Lact > 0 was associated with an increase in overall intensive care unit morbidity. An independent relationship was also found between ∆Lact and 30-day mortality as of a 1 mmol L−1 increase.
Our results suggest that ∆Lact is associated with poor short-term outcomes in adult cardiac surgical patients.
Cardiopulmonary bypass causes detrimental effects on remote organs due to inflammatory response. One of these organs is kidney that is frequently affected by cardiac surgery. Acute kidney injury is a post-cardiopulmonary bypass complication, which may result in increased post-operative morbidity and mortality. Post-cardiopulmonary bypass inflammatory response may contribute to remote organ dysfunction. In the present study, we investigated the relation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α, and renal function tests such as creatinine and blood urea nitrogen (BUN).
In total, 91 patients between the ages of 4 and 60 months were enrolled for elective cardiac surgery with cardiopulmonary bypass after informed consent. Data regarding renal function tests and clinical outcomes were carefully recorded until 24 hours after admission to intensive care unit and analyzed.
Our findings support that there is a direct correlation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α and cardiopulmonary bypass time, duration of operation, and intensive care unit stay. Longer cardiopulmonary bypass time was associated with higher interleukin-8 at cross-clamp removal and 24 hours post- intensive care unit as well as higher interleukin-10 at declamp time. Higher interleukin-6 at declamp time was directly correlated with higher post-operative BUN. Interleukin-8 level after anesthesia induction was directly correlated with intensive care unit stay duration. Higher blood interleukin-6 and tumor necrosis factor-α levels following 24 hours of admission to intensive care unit were associated with longer mechanical ventilation time.
Higher circulatory pro-inflammatory cytokine level is associated with adverse outcomes such as increased intensive care unit stay and longer mechanical ventilation time in pediatric patients. It is also correlated with unfavorable biochemical parameter of renal function, BUN. Findings hint that proper control of the inflammatory response is vital for the control of unfavorable clinical and pathological outcomes.
Blastomyces is a dimorphic fungus endemic to regions of North America, which can lead to pneumonia and fatal severe acute respiratory diseases syndrome in up to 89% of patients. Extracorporeal life support can provide adequate oxygenation while allowing the lungs to rest and heal, which might be an ideal therapy in this patient group, although long-term clinical and radiological outcomes are not known.
We report on five consecutive patients admitted to Toronto General Hospital intensive care unit between January 2012 and September 2016, with progressive respiratory failure requiring veno-venous extracorporeal life support within 24-96 hours following mechanical ventilation. Ultra-lung protective mechanical ventilation was achieved within 24 hours. Recovery was the initial goal in all patients. Extracorporeal life support was provided for a prolonged period (up to 49 days), and four patients were successfully discharged from the intensive care unit. Long-term radiological assessment in three patients showed major improvement within 2 years of follow-up with some persistent disease-related changes (bronchiectasis, fibrosis, and cystic changes). In two patients, long-term functional and neuropsychological outcomes showed similar limitations to what is seen in acute respiratory distress syndrome patients who are not supported with extracorporeal life support and in acute respiratory distress syndrome patients without blastomycosis, but worse pulmonary function outcomes in the form of obstructive and restrictive changes that correlated with the radiological imaging.
Veno-venous extracorporeal life support can effectively provide prolonged support for patients with blastomycosis-associated acute respiratory distress syndrome that is safe and associated with favorable long-term outcomes.
Extracorporeal membrane oxygenation mandates balancing the risk of thromboembolic complications with bleeding. We aimed to evaluate pragmatic anticoagulation regimens during extracorporeal membrane oxygenation and compare thromboembolic and bleeding outcomes.
This retrospective, single-center study reviewed patients on venovenous or venoarterial extracorporeal membrane oxygenation for a minimum of 24 hours over a 5-year period. The primary outcome was composite thromboembolic events per day of extracorporeal membrane oxygenation. Secondary outcomes included composite bleeding complications, percent of measured activated partial thromboplastin times in goal range, and comparing events with therapeutic anticoagulation for the majority of the extracorporeal membrane oxygenation run (>50% of time on extracorporeal membrane oxygenation) versus non-therapeutic anticoagulation (therapeutic anticoagulation <50% of time).
For the primary analysis, 100 patients received heparin, 10 received bivalirudin, and 43 were transitioned between heparin and bivalirudin. No significant differences were identified comparing the heparin group to the bivalirudin (RR = 0.427, p = 0.156) or transitioned group (RR = 1.274, p = 0.325). There were no differences in the rate of bleeding events when comparing the heparin group to the bivalirudin (RR = 0.626, p = 0.250) or transitioned group (RR = 0.742, p = 0.116). An increased number of adjustments to the anticoagulants was associated with a statistically higher rate of bleeding events per day (p = 0.006).
There were no differences in thromboembolic or bleeding events when comparing different anticoagulant regimens. Adjustments to the anticoagulants are more likely to occur when bleeding is observed. Due to variability in anticoagulation, there is a need to standardize anticoagulation with extracorporeal membrane oxygenation.
The purpose of this cohort study was to investigate the independent relationship between euthyroid sick syndrome and in-hospital outcomes in high-risk patients undergoing isolated coronary artery bypass grafting, and we also examined the direct correlation between pre- or intra-operative variables and the incidence of coronary artery bypass grafting–associated euthyroid sick syndrome.
The present study enrolled high-risk patients undergoing coronary artery bypass grafting from 1 January 2017 to 31 December 2017 in Beijing Anzhen hospital, including 387 (58.7%) patients with coronary artery bypass grafting–associated euthyroid sick syndrome and 272 (41.3%) patients without coronary artery bypass grafting–associated euthyroid sick syndrome.
The mean age of euthyroid sick syndrome group was significantly older than that of no euthyroid sick syndrome group (65.9 ± 7.5 vs 60.9 ± 9.6, p < 0.0001). Compared with the control group, significantly higher proportions of patients with euthyroid sick syndrome had presented with the following clinical characteristics at hospital admission: moderate and poor left ventricular ejection fraction (42.9% vs 28.7%, p < 0.0001), higher euroscore II (9.2 ± 4.1 vs 8.0 ± 3.9, p < 0.0001). Multivariate logistic regression analysis on the total patients revealed that the independent risk factors for coronary artery bypass grafting–associated euthyroid sick syndrome were advanced age (odds ratio = 1.07, 95% confidence interval = 1.05-1.09, p < 0.0001), higher euroscore II (odds ratio = 1.06, 95% confidence interval = 1.01-1.11, p = 0.013), and moderate and poor left ventricular ejection fraction (odds ratio = 2.26, 95% confidence interval = 1.61-3.18, p < 0.0001). Furthermore, euthyroid sick syndrome was independently correlated with an increased risk of in-hospital major adverse cardiovascular and cerebral events (odds ratio = 3.40, 95% confidence interval = 1.64-7.02, p = 0.001) and post-infection (odds ratio = 8.11, 95% confidence interval = 3.97-16.57, p < 0.0001) Besides, we also confirmed coronary artery bypass grafting–associated euthyroid sick syndrome was associated with Sequential Organ Failure Assessment maximum greater than 11 (odds ratio = 2.98, 95% confidence interval = 1.90-4.65, p < 0.0001), which predicted an in-hospital death rate of 95%, independently.
Coronary artery bypass grafting–associated euthyroid sick syndrome exerted detrimental effects on short-term clinical outcomes in high-risk patients undergoing isolated coronary artery bypass grafting. Advanced age, higher euroscore II, and moderate and poor left ventricular ejection fraction were independent risk factors for coronary artery bypass grafting–associated euthyroid sick syndrome.
Veno-arterial extracorporeal membrane oxygenation represents the last therapy option in refractory cardiogenic shock. Successful weaning becomes difficult if the myocardial function recovers but pulmonary impairment persists. We present our experience with a new weaning strategy, using a stepwise mode-switch from veno-arterial to veno-veno-arterial and veno-venous extracorporeal membrane oxygenation setting for patients with primary cardiogenic shock and subsequent respiratory failure.
From 81 patients treated with veno-arterial extracorporeal membrane oxygenation following acute cardiogenic shock between January 2014 and April 2018, eight patients with cardiac and pulmonary failure were identified to be treated using the following protocol: patients were put on veno-arterial extracorporeal membrane oxygenation, a second inflow cannula was inserted via the right jugular vein and cardiac weaning was performed via veno-veno-arterial support. Finally, patients were pulmonary weaned via veno-venous extracorporeal membrane oxygenation mode.
In the mode-switch group, etiologies of cardiogenic shock were cardiac arrest (12.5%), myocardial infarction (12.5%) and post-cardiotomic heart failure (75%). Mean time between onset of cardiogenic shock and start of veno-arterial extracorporeal membrane oxygenation was 76 ± 117 min. At implantation, lactate and pH values were 9.5 ± 5.0 mmol/L and 7.2 ± 0.2. Total extracorporeal membrane oxygenation-time was 9.3 ± 4.7 days, with a mode-switch from veno-arterial to veno-veno-arterial after 3.9 ± 2.7 days. The weaning rate in the mode-switch group was 75% (vs. 41% in the entire cohort) and the 30-day survival was 50% (vs 32% in the cohort). 38% of the patients presented a favorable neurological outcome.
Mode-switch from veno-arterial to veno-veno-arterial and weaning via veno-venous extracorporeal membrane oxygenation mode is feasible for combined cardiac and pulmonary failure, with promising results due to an optimized pre-pulmonary oxygenation.
The present study aimed to examine whether GATA-4 overexpressing bone marrow mesenchymal stem cells can improve cardiac function in a murine myocardial infarction model compared with bone marrow mesenchymal stem cells alone.
A lentiviral-based transgenic system was used to generate bone mesenchymal stem cells which stably expressed GATA-4 (GATA-4-bone marrow mesenchymal stem cells). Apoptosis and the myogenic phenotype of the bone marrow mesenchymal stem cells were measured using Western blot and immunofluorescence assays co-cultured with cardiomyocytes. Cardiac function, bone marrow mesenchymal stem cell homing, cardiac cell apoptosis, and vessel number following transplantation were assessed, as well as the expression of c-Kit.
In GATA-4-bone marrow mesenchymal stem cells-cardiomyocyte co-cultures, expression of myocardial-specific antigens, cTnT, connexin-43, desmin, and α-actin was increased compared with bone marrow mesenchymal stem cells alone. Caspase 8 and cytochrome C expression was lower, and the apoptotic rate was significantly lower in GATA-4 bone marrow mesenchymal stem cells. Cardiac function following myocardial infarction was also increased in the GATA-4 bone marrow mesenchymal stem cell group as demonstrated by enhanced ejection fraction and left ventricular fractional shortening. Analysis of the cardiac tissue revealed that the GATA-4 bone marrow mesenchymal stem cell group had a greater number of DiR-positive cells suggestive of increased homing and/or survival. Transplantation with GATA-4-bone marrow mesenchymal stem cells significantly increased the number of blood vessels, decreased the proportion of apoptotic cells, and increased the mean number of cardiac c-kit-positive cells.
GATA-4 overexpression in bone marrow mesenchymal stem cells exerts anti-apoptotic effects by targeting cytochrome C and Fas pathways, promotes the aggregation of bone marrow mesenchymal stem cells in cardiac tissue, facilitates angiogenesis, and effectively mobilizes c-kit-positive cells following myocardial infarction, leading to the improvement of cardiac function after MI.
A minimal volume ventilation method for robotically assisted mitral valve surgery is described in this study. In an attempt to reduce postoperative pulmonary dysfunction, 40 of 174 patients undergoing robotically assisted mitral valve surgery were ventilated with a small tidal volume during cardiopulmonary bypass.
After propensity score matching, 31 patients with minimal volume ventilation were compared with 54 patients with no ventilation. Total ventilation time, PaO2/FiO2 ratio, arterial lactate concentration, and the rate of unilateral pulmonary edema in the matched minimal ventilation and standard treatment groups were evaluated.
Patients in the minimal ventilation group had shorter ventilation times, 12.0 (interquartile range: 9.9-15.0) versus 14.0 (interquartile range: 12.0-16.3) hours (p = 0.036), and lower postoperative arterial lactate levels, 0.99 (interquartile range: 0.81-1.39) versus 1.28 (interquartile range: 0.99-1.86) mmol/L (p = 0.01), in comparison to patients in the standard treatment group. There was no difference in postoperative PaO2/FiO2 ratio levels or in the rate of unilateral pulmonary edema between the groups.
Minimal ventilation appeared beneficial in terms of total ventilation time and blood lactatemia, while there was no improvement in arterial blood gas measurements or in the rate of unilateral pulmonary edema. The lower postoperative arterial lactate levels may suggest improved lung perfusion among patients in the minimal volume ventilation group. The differences in the ventilation times were in fact small, and further studies are required to confirm the possible advantages of the minimal volume ventilation method in robotically assisted cardiac surgery.
Targeted temperature management and extracorporeal life support, particularly extracorporeal membrane oxygenation in patients undergoing cardiopulmonary resuscitation, represent outcome-enhancing strategies for patients following in- and out-of-hospital cardiac arrest. Although targeted temperature management with hypothermia between 32°C and 34°C and extracorporeal cardiopulmonary resuscitation bear separate potentials to improve outcome after out-of-hospital cardiac arrest, each is associated with bleeding risk and risk of infection. Whether the combination imposes excessive risk on patients is, however, unknown.
In recent years, extracorporeal membrane oxygenation has become increasingly common in the treatment of in-hospital cardiac arrest in non-cardiac surgery patients. This includes cardiac arrest secondary to perioperative anaphylactic shock refractory to standard advanced life support protocols, which is a rare but catastrophic event associated with significant mortality. Neuromuscular blocking drugs are most commonly implicated in perioperative anaphylaxis, with rocuronium playing a major role. In this article, we report two cases of young and otherwise fit and well patients who experienced a perioperative arrest secondary to rocuronium anaphylaxis before elective surgery; both patients did not respond to conventional advanced life support, but survived neurologically intact after institution of urgent veno-arterial extracorporeal membrane oxygenation.