Off-Pump Conversion: In-hospital Mortality and Long-Term Survival.

Background There is an ongoing debate on the benefits and risks of off-pump coronary artery bypass grafting (CABG) surgery. The fate of patients who start with their procedure being an off-pump one and then have to undergo conversion to an on-pump procedure is debated with regard to in-hospital mortality and unknown with regard to long-term survival. We investigated the in-hospital mortality and long-term survival of patients who underwent conversion from off- to on-pump surgery. Methods We performed a multivariate and propensity analysis on in-hospital mortality and long-term survival of postisolated CABG patients in a single institution having 15,704 patients of which 5,353 who underwent off-pump CABG were analyzed. Results In-hospital mortality was 2.15% for the study cohort, and 73 (1.4%) off-pump cases were converted. Univariate analysis demonstrated that patients undergoing conversion had a significantly increased in-hospital mortality (p < 0.001) and reduced long-term survival (p = 0.002). Logistic regression (receiver operating curve 0.77, Hosmer-Lemeshow test 0.46) and Cox analysis demonstrated that in-hospital mortality and long-term survival were not significantly affected by conversion. Propensity analysis (one:many match) demonstrated that in-hospital mortality was not significantly affected (p = 0.7), and long-term survival - univariate, and multivariate were also not significantly reduced in patients undergoing conversion. Conclusion Conversion from off- to on-pump by a team of surgeons and anesthetists who are dedicated off-pump specialists does not have an impact on in-hospital mortality or long-term survival.

Report from AmSECT's International Consortium for Evidence- Based Perfusion Consensus Statement: Minimal Criteria for Reporting Cardiopulmonary Bypass-Related Contributions to Red Blood Cell Transfusions Associated With Adult Cardiac Surgery.

Gaps remain in our understanding of the contribution of bypass-related practices associated with red blood cell (RBC) transfusions after cardiac surgery. Variability exists in the reporting of bypass-related practices in the peer-reviewed literature. In an effort to create uniformity in reporting, a draft statement outlining proposed minimal criteria for reporting cardiopulmonary bypass (CPB)- related contributions (i.e., RBC data collection/documentation, clinical considerations for transfusions, equipment details, and clinical endpoints) was presented in conjunction with the American Society of ExtraCorporeal Technology's (AmSECT's) 2014 Quality and Outcomes Meeting (Baltimore, MD). Based on presentations and feedback from the conference, coauthors (n = 14) developed and subsequently voted on each proposed data element. Data elements receiving a total of 4 votes were dropped from further consideration, 5-9 votes were considered as "Recommended," and elements receiving ≥10 votes were considered as "Mandatory." A total of 52 elements were classified as mandatory, 16 recommended, and 14 dropped. There are 8 mandatory data elements for RBC data collection/documentation, 24 for clinical considerations for transfusions, 13 for equipment details, and 7 for clinical endpoints. We present 52 mandatory data elements reflecting CPB-related contributions to RBC transfusions. Consistency of such reporting would offer our community an increased opportunity to shed light on the relationship between intra-operative practices and RBC transfusions.

Computational fluid dynamic analysis to prevent aortic root and valve clots during left ventricular assist device support.

Aortic root and valve clots are rare but well described in patients on maximal left ventricular assist device (LVAD) support. We performed a theoretical analysis using computational fluid dynamic analyses in two dimensions to try and ascertain if inflow cannula design/orientation/placement affect aortic root flow dynamics. Two-dimensional computational fluid dynamics using easy CFD-G was performed. The effect of a curved inflow cannula, a straight cannula, and one with a hole in the outer curve was analyzed. In addition, the effect of inflow conduit angulation on the ascending aorta was studied. Computational fluid dynamic (CFD) analysis predicts that stagnant blood exists in the aortic root when little or no cardiac ejection is taking place. Coronary flow is too small to affect the root flow streamlines. A hole on the root side of a curved inflow aortic cannula increases the flow in the aortic root and may decrease the incidence of root and valve thrombosis. The angle of the inflow conduit attachment to the ascending aorta was also found to be crucial with regard to aortic root blood stasis. In addition, a baffle at the tip of the inflow cannula may prove to be beneficial. Theoretical analysis using the technique of CFD predicts that inflow cannula position and design may affect the incidence of aortic root thrombosis during LVAD support when minimal cardiac ejection is occurring.

Heparin therapy during extracorporeal circulation: deriving an optimal activated clotting time during cardiopulmonary bypass for isolated coronary artery bypass grafting.

Bull's seminal work on heparin therapy during cardiopulmonary bypass (CPB) was carried out over 30 years ago and has not been updated in the modern era. No correlation with postoperative blood loss was performed. The optimal activated clotting time (ACT) with regard to blood loss has not been established for patients undergoing CPB. A minimum ACT of 400 is based on the lack of visible formation of clots in the CPB circuit. The effect of heparin dose, sensitivity, metabolism, patient size, elective/urgent, protamine reversal regime, returned pump blood volume and heparin content, and average ACT during CPB with regard to postoperative blood loss and resternotomy was examined in a consecutive series of patients undergoing isolated coronary artery bypass surgery. One hundred forty-four patients undergoing isolated CABG were studied. Resternotomy was too infrequent an event to analyze. Univariate analysis revealed that an average ACT less than 500 or greater than 700 was associated with significantly increased postoperative blood loss (p = .001). Multivariate analyses revealed that body mass index (p < .0001) and total loading dose of heparin (p = .0031) were also significant factors affecting postoperative blood loss. We extended his work by analyzing postoperative blood loss. An average ACT between 500 and 700 in our series was associated with significantly lower blood loss than an ACT higher or lower. We hypothesize that an ACT below 500 is probably associated with a low-grade coagulopathy but not macroscopic clot formation in the CPB circuit, and above 700 heparin rebound may become important. Each unit should evaluate blood loss and determine the optimal ACT target for their program.

Theoretical treatise: arterial pressure during aortic surgery.

The optimum arterial perfusion pressure during cardiopulmonary bypass (CPB) remains uncertain. A correlation in some form with the patients' resting pressure almost certainly exists. Temperature and hematocrit affect blood viscosity. The optimum perfusion pressure during aortic surgery will vary after the initiation of CPB resulting cooling, heating, and hematocrit changes. Poiseuille's Law was used in conjunction with the previously published effects of temperature and hematocrit on blood viscosity to determine the perfusion pressure that would result in the same organ blood flow. Two different scenarios were modeled, constant flow and flow as predicted by Q10 to reflect required oxygen delivery. Temperature, hematocrit, and flow all have a large effect on blood viscosity and, thus, through Poiseuille's Law, blood pressure. As patients are cooled, their blood viscosity goes up through the inherent viscoelastic properties of blood. As temperature drops from 37 degrees to 17 degrees, viscosity doubles. This increased viscosity is offset by a reduction in hematocrit, which is invariably associated with CPB. As the hematocrit drops from 30% to 10%, viscosity of blood halves. These two factors clinically can cancel each other out. The figure demonstrates the effect on blood pressure of a constant flow for various temperature and hematocrits. Reduced need for oxygen delivery, secondary to the principles of Q10, can result in a lower than expected theoretical perfusion pressure. As temperature drops from 37 degrees to 17 degrees, based on Q10, oxygen delivery reduces by 75%. This indicates that flow can be reduced by over 60% if the hematocrit falls from 30% to 20%. This theoretical treatise predicts that blood pressure management should be temperature- and hematocrit-dependent. The target optimal blood pressure will vary during the course of surgery as a result of heating, cooling, and hemodilution. Clinical correlation is needed.

Lissajous figures: an engineering tool for root cause analysis of individual cases--a preliminary concept.

Some patients have short intensive care stay periods and little or no organ dysfunction after cardiac surgery and others do not despite seemingly faultless surgery, perfusion, and anesthesia. These "unknown" reasons for death and morbidity usually relate to organ ischemia and inflammation, but are obviously mutlifactorial. A Lissajous figure is a technique in electrical engineering to compare two different electrical signals. We utilize this basic concept in a very simple manner to potentially identify why some of these unknown deaths or morbidities occur. Utilizing an electronic perfusion database, we retrospectively analyzed 43 patients undergoing aortic surgery with regard to central venous saturations during cooling and rewarming. Isolated aortic valve replacement patients were excluded. Central venous saturation, time, and temperature were plotted to create a Lissajous figure for the whole operation, and during cooling and rewarming separately. Temperature and saturations were analyzed every 20 seconds. Perfusion related variables were registered and uploaded to www.perfsort.net. Lissajous figures during cooling add little to patient care due to their similarity. Isolated rewarming revealed startling differences. It is immediately visually obvious who had short and long periods of tissue ischemia and reperfusion during rewarming in a seemingly uneventful operation. The periods of ischemia can be semi quantified into: none, mild, moderate, and severe. Creation of simple Lissajous figures during rewarming for bypass runs may be an additional helpful tool in root cause analysis of patient death/morbidity when surgery, perfusion, and anesthesia seemed faultless. Low central venous saturations at hypothermic temperatures mean significant metabolic activity, indicating tissue ischemia is occurring. Further work is needed to correlate this concept to outcomes.

Consensus statement: minimal criteria for reporting the systemic inflammatory response to cardiopulmonary bypass.

The lack of established cause and effect between putative mediators of inflammation and adverse clinical outcomes has been responsible for many failed anti-inflammatory interventions in cardiopulmonary bypass (CPB). Candidate interventions that impress in preclinical trials by suppressing a given inflammation marker might fail at the clinical trial stage because the marker of interest is not linked causally to an adverse outcome. Alternatively, there exist examples in which pharmaceutical agents or other interventions improve clinical outcomes but for which we are uncertain of any antiinflammatory mechanism. The Outcomes consensus panel made 3 recommendations in 2009 for the conduct of clinical trials focused on the systemic inflammatory response. This panel was tasked with updating, as well as simplifying, a previous consensus statement. The present recommendations for investigators are the following: (1) Measure at least 1 inflammation marker, defined in broad terms; (2) measure at least 1clinical end point, drawn from a list of practical yet clinically meaningful end points suggested by the consensus panel; and(3) report a core set of CPB and perfusion criteria that maybe linked to outcomes. Our collective belief is that adhering to these simple consensus recommendations will help define the influence of CPB practice on the systemic inflammatory response, advance our understanding of causal inflammatory mechanisms, and standardize the reporting of research findings in the peer-reviewed literature.

Preoperative hyponatremia and cardiopulmonary bypass: yet another factor for cerebral dysfunction?

Hyponatremia is common in patients prior to cardiopulmonary bypass (CPB), usually secondary to diuretic therapy. Rapid correction of chronic hyponatremia, which potentially occurs on commencing CPB, may in susceptible patients result in central pontine myelomatosis. There are three parts to this study. Part 1: Patients (n = 170) undergoing CPB with preoperative hyponatremia were analyzed by degree of hyponatremia, additive EuroSCORE, length of stay - intensive care and total hospital, and mortality. Part 2: Sodium concentrations of different prime constituents used clinically were collated from the literature. Part 3: Mathematical modeling of the effects of patient size, sex, preoperative hemoglobin, prime solution, and prime volume with regard to the effect on serum sodium during cardiopulmonary bypass was analyzed, assuming a preoperative serum sodium of 125 mmol/L. Part 1: Patients with preoperative hyponatremia, even after matching by additive EuroSCORE, have longer length of stay - intensive care and total hospital, but not significantly different mortality rates. Part 2: Sodium concentrations of different primes used clinically varied from 0 mmol/L to 160 mmol/L. Part 3: Mathematical modeling revealed that patient size, sex, preoperative hemoglobin, prime solution, and prime volume all can exert a significant effect on serum sodium on initiation of cardiopulmonary bypass. Further work is needed to evaluate the roles of sudden changes in serum sodium, with regard to a rapid correction of chronic hyponatremia, or the rapid creation of acute hyponatremia, and cerebral outcomes in patients undergoing CPB.

Patient directed perfusion pressure on bypass, an analogy from electrical engineering--a new concept.

Organ ischemia, particularly mesenteric and renal, can occur despite a seemingly adequate perfusion flow and pressure during a period of cardiopulmonary bypass. The blood pressure to run bypass at remains a contentious issue. We present the concept that perfusion pressure during cardiopulmonary bypass should be patient specific, depending on an individual's resting pre-procedural blood pressure. Four simulated arterial traces with variable morphology, but identical systolic and diastolic blood pressures, were analyzed to calculate the medical mean, arithmetic mean, and root mean square of the blood pressure tracing. Using the standard medical formula for calculation of mean blood pressure, you can potentially underestimate perfusion pressure by 12 mmHg in a normotensive subject. The root mean square pressure calculates the equivalent non pulsatile pressure that will deliver the same hydraulic power to the circulation as its pulsatile equivalent. Patient specific perfusion pressures, calculated via root mean square may potentially help reduce the incidence of organ ischemia during cardiopulmonary bypass. Clinical trials are needed to confirm or refute this concept.

Patient directed bypass: cooling for aortic surgery--a preliminary concept.

No consensus exists as to the temperature to cool to on bypass for surgery involving the aortic arch. Excluding normothermic surgery, which is rarely performed for arch work, circulatory arrest, anterograde, and retrograde cerebral perfusion either in isolation or in combination remain the techniques of "cerebral protection." To date, no account of individual patient body or cerebral function variation is involved. Utilizing an electronic perfusion database we retrospectively analyzed 10 patients undergoing aortic arch work with regard to mixed venous saturations during cooling. Perfusion related variables were registered and uploaded to www.perfsort.net. We regarded a saturation of 100% as being indicative of no oxygen extraction, implying no metabolic activity--the theoretical goal prior to a circulatory arrest period. There is enormous variation in the temperature at which metabolic activity of the body stops. We had a range from 17-25 degrees. Patients were cooled for an average of 6 (SD 3.4) degrees below which oxygen extraction had ceased to occur. Potentially we are adding 111 minutes (SD 62) of unnecessary bypass time. This may imply that excessive cooling is occurring in some individuals undergoing arch surgery. Patient directed cooling for aortic arch surgery may help to reduce the morbidity/physical insult associated with severe hypothermia. This work is very preliminary but may help us to depart from the one size fits all paradigm that exists in current clinical practice. Correlation with bispectral index, electroencephalogram monitoring and neurological outcomes is needed.

Composite endpoints: What were the odds of that?

Composite endpoints are frequently utilised in clinical studies. The creation of composite endpoints in their current form, a death carries the same weight as for example a stroke, repeat revascularisation or myocardial infarction. We hypothesise that the non-death terms of a composite score should be created such that the factor involved is weighted via odds ratios for its risk of association with death. We explore and demonstrate this using previously published odds ratios for these factors, and apply it to a hypothetical trial similar to Excel, to demonstrate the principle. The same principle could be applied to composite survival endpoints, when the factors are weighted via hazard ratios.

Mathematical modeling in cardiac surgery: helping clinical trials answer the question.

Mathematical modeling, based on fundamental principles from engineering may help clinical trial design, aiding in answering problems that remain in cardiac surgery, such as management of carotid artery stenosis in patients undergoing cardiopulmonary bypass (CPB), hematocrit during CPB, adequacy of oxygen delivery during CPB, adequacy of blood pressure management during CPB, filtration during bypass for renal failure, bypass circuit pacification, carbon dioxide wound insufflation and neurological events, and pulsatile to nonpulsatile flow during CPB. In addition, mathematical modeling may help explain deficiencies of previous work that have failed to clarify what to do.

Effect of foreign surface pacification with albumin, aprotinin, propofol, and high-density lipoprotein.

Foreign surface pacification may significantly reduce the detrimental effects of the cardiopulmonary bypass (CPB) circuit. To date, albumin is the only intervention consistently shown to be beneficial. The cationic physical properties of aprotinin and the known negative charge on the plastic CPB circuit mean that aprotinin binds to the CPB circuit and membrane oxygenator. A previously validated model involving a parallel plate glass slide technique was used. The effects of albumin, aprotinin, propofol, and high-density lipoprotein (HDL) were assessed by the ability to inhibit platelet adhesion to the glass slide surface. The experiment was repeated with collagen-coated glass slides to reproduce the clinical effect of endothelial denudation. The interventions were repeated on membrane oxygenators that are used for CPB. Aprotinin resulted in a minimal reduction in platelet adhesion to uncoated or collagen-coated glass slides. HDL significantly reduced platelet adhesiveness to uncoated or collagen-coated glass slides. Human albumin solution (HAS) and propofol produced an intermediary inhibitory effect on platelet adhesion on both collagen-coated and uncoated glass slides. The same effect was seen with membrane oxygenators that are used during CPB. HDL produced a significant reduction of neutrophil activation when used to coat a membrane oxygenator. Foreign surface pacification with HDL may have beneficial effects as assessed by platelet adhesiveness in a parallel plate assay. Aprotinin had minimal effect, and propofol had an intermediate effect. The same results were obtained using membrane oxygenators, confirming the validity of the parallel plate technique as clinically valid.

Carotid artery diameter, plaque morphology, and hematocrit, in addition to percentage stenosis, predict reduced cerebral perfusion pressure during cardiopulmonary bypass: a mathematical model.

Cerebral complications after cardiac surgery are a significant cause of morbidity, mortality, and financial cost. Numerous risk factors have been proposed to explain the risk of cerebral damage. Carotid artery disease has an important role. Percentage carotid artery stenosis is the only measure of carotid artery disease that is used by cardiac surgeons to determine the need for either a carotid endarterectomy and/or a higher pump perfusion pressure. Identification of patients through their carotid plaque morphology who might benefit from higher pump perfusion pressures or concomitant carotid endarterectomy may reduce cerebral morbidity and mortality. A mathematical model using finite element analysis was created to model the carotid artery vessel and its stenotic plaque. Analysis showed that the degree of carotid artery stenosis, the length of the carotid artery plaque, the diameter of the carotid artery, and the blood hematocrit all independently significantly affect the required pump perfusion pressure to maintain adequate cerebral perfusion during cardiopulmonary bypass (CPB). The results from a mathematical model showed that carotid artery diameter, carotid artery plaque length, and hematocrit, in addition to percentage stenosis, should be included in any thought process involving carotid artery stenosis and cardiac surgery. Estimating cerebral risk during CPB should no longer rely on only the percentage stenosis.