Measurement of total hemoglobin reduces red cell transfusion in hospitalized patients undergoing cardiac surgery: a retrospective database analysis.

INTRODUCTION: Historically, perioperative hemoglobin monitoring has relied on calculated saturation, using blood gas devices that measure plasma hematocrit (Hct). Co-oximetry, which measures total hemoglobin (tHb), yields a more comprehensive assessment of hemodilution. The purpose of this study was to examine the association of tHb measurement by co-oximetry and Hct, using conductivity with red blood cell (RBC) transfusion, length of stay (LOS) and inpatient costs in patients having major cardiac surgery. METHODS: A retrospective study was conducted on patients who underwent coronary artery bypass graft (CABG) and/or valve replacement (VR) procedures from January 2014 to June 2016, using MedAssets discharge data. The patient population was sub-divided by the measurement modality (tHb and Hct), using detailed billing records and Current Procedural Terminology coding. Cost was calculated using hospital-specific cost-to-charge ratios. Multivariable logistic regression was performed to identify significant drivers of RBC transfusion and resource utilization. RESULTS: The study population included 18,169 cardiovascular surgery patients. Hct-monitored patients accounted for 66% of the population and were more likely to have dual CABG and VR procedures (10.4% vs 8.9%, p=0.0069). After controlling for patient and hospital characteristics, as well as patient comorbidities, Hct-monitored patients had significantly higher RBC transfusion risk (OR=1.26, CI 1.15-1.38, p<0.0001), longer LOS (IRR=1.08, p<0.0001) and higher costs (IRR=1.15, p<0.0001) than tHb-monitored patients. RBC transfusions were a significant driver of LOS (IRR=1.25, p<0.0001) and cost (IRR=1.22, p<0.0001). CONCLUSIONS: tHb monitoring during cardiovascular surgery could offer a significant reduction in RBC transfusion, length of stay and hospital cost compared to Hct monitoring.

Endothelial Glycocalyx and Cardiopulmonary Bypass.

On the outer surface of a human cell there is a dense layer of complex carbohydrates called glycocalyx, also referred to as glycans or the sugar coating on the cell surface, which is composed of a complex array of oligosaccharide and polysaccharide glucose chains that are covalently bonded to proteoglycans and lipids bound to the cell membrane surface. Studies of an intact endothelial glycocalyx layer (EGL) have revealed a number of critical functions that relate the importance of this protective layer to vascular integrity and permeability. These functions include the following: stabilization and maintenance of the vascular endothelium, an active reservoir of essential plasma proteins (i.e., albumin, antithrombin, heparan sulfate, and antioxidants), a buffer zone between the blood (formed elements) and the surface of the endothelium, and a mechanotransducer to detect changes in shear stress that facilitate vascular tone. There have been numerous review articles about the structure and function of endothelial glycocalyx over the past two decades, yet there still remains a significant knowledge gap in the perfusion literature around the importance of EGL. Perioperative fluid management and gaseous microemboli can both contribute to the damage/degradation of endothelial glycocalyx. A damaged EGL can result in systemic and myocardial edema, platelet and leukocyte adhesion, fluid extravasation, and contributes to microvascular perfusion heterogeneity. Knowledge of the importance of endothelial glycocalyx will enable clinicians to have a better understanding of the impact of gaseous microbubbles, hyperoxia, and ischemic reperfusion injury during cardiac surgery. The purpose of this article is to provide an in depth review of the EGL and how this protective barrier impacts the microcirculation, fluid homeostasis, inflammation, and edema during cardiac surgery.

Understanding Off-Label Use and Reference Blood Flows in Modern Membrane Oxygenators.

This editorial will address two issues that are still a source of global controversy and confusion in present day perfusion practice. Membrane oxygenators are designed and tested to a set of stringent flow standards prior to their release from every manufacturer. But how well do we know the iatrogenic consequences of pushing these devices beyond their maximum rated limits? In addition, how well do we know the meaning of the term 'AAMI Reference Flow' as it relates to the Manufacturers Maximum Rated Flow?

Arterial filter bypass loop: what occurs in this area during cardiopulmonary bypass and are there potential patient implications.

The arterial filter is an integral part of bypass circuitry. When introduced, manufacturers suggested a bypass loop for retrograde priming and de-airing, and for uninterrupted blood flow in case of malfunction. Practice has shown antegrade priming and de-airing is possible. This questions the necessity of the loop and presents the question-what occurs in the loop during bypass? After obtaining Human Research Ethics Board approval, eight consecutive patients (n = 8) were chosen for this study. Exclusive exclusion criterion was receiving any transfusions during cardiopulmonary bypass, as this could possibly influence results. The choice of patient numbers was based simply on proof of concept. Investigation involved isolation and collection of loop contents after cardiopulmonary bypass was completed. Testing included complete blood count, prothrombin time, international normalized ratio, partial thromboplastin time, activated clotting time, plasma free hemoglobin, slide photography with analysis for platelet clumping, and debris detection. One perfusionist collected samples, providing uniform collection and isolation technique. Regular blood samples were collected from the bypass circuitry, and from patients' pre-operative blood work. Analysis of data revealed that platelet counts in the bypass loops were statistically lower than control. Evidence of platelet clumping was present in 3 of 8 bypass loop samples, representing 37.5% of the study population. There was no clumping detected in any of the controls. In patients where platelet clumping was present, a positive correlation was noted between mean bypass time and size of platelet clumps. Prothrombin time and international normalized ratio results were immeasurable. Hemoglobin levels were higher in the loop samples. There was no evidence of debris or fibrin monomer present in any of the samples analyzed. The study results indicate that during "normal" cardiopulmonary bypass with an arterial filter bypass loop, platelet aggregates can accumulate in the loop, therefore opening the arterial bypass loop in any case may subject the patient to micro/macro emboli.

Rationale and use of perfusion variables in the 2010 update of the society of thoracic surgeons congenital heart surgery database.

Patients undergoing congenital heart surgery are at risk of morbidity and mortality. The reasons underlying this risk are complex. To identify opportunities to reduce adverse sequelae, the cardiovascular perfusion community was invited to amend existing perfusion-related fields as well as add new ones to the current version of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD). The International Consortium for Evidence-Based Perfusion (ICEBP) was invited by the STS-CHSD Task Force to identify and resolve ambiguities related to definitions among the 3 current perfusion-related fields as well as to propose new variables (and definitions) for inclusion in the 2010 update of the STS-CHSD. The ICEBP used teleconferences, wiki-based communication software, and e-mail to discuss current definitions and create new fields with definitions. The ICEBP created modified definitions to existing fields related to cardiovascular perfusion and also developed and defined new fields that focus on (1) techniques of circulatory arrest and cerebral perfusion, (2) strategies of myocardial protection, and (3) techniques to minimize hemodilution and allogeneic blood transfusions. Three fields in the STS-CHSD related to perfusion were redefined, and 23 new variables and definitions were selected for inclusion. Identifying and defining fields specific to the practice of perfusion are requisite for assessing and subsequently improving the care provided to patients undergoing congenital heart surgery. The article describes the methods and justification for adjudicating extant and new perfusion-related fields added to the 2010 update of the STS-CHSD.

The effect of Diprivan (propofol) on phosphorylcholine surfaces during cardiopulmonary bypass--an in vitro investigation.

It is well known that extracorporeal surfaces have the ability to bind such drugs as fentanyl, nitroglycerine and propofol. Adsorption of the injectable anesthetic agent Diprivan (propofol) onto uncoated and heparin-coated extracorporeal surfaces during cardiopulmonary bypass (CPB) has been previously investigated; however, propofol adsorption onto synthetic-coated extracorporeal surfaces has not been published previously. The focus of this investigation was on the interaction of propofol and the synthetic biomimetic coating from the Sorin Group called Mimesys (phosphorylcholine (PC)). A randomized series of six in vitro experiments were done with propofol using both PC-coated circuits without arterial filters and those with arterial filters. The circuits were identical in all experiments and priming remained the same, with 750 mls of normal saline and 1250 mls of fresh bovine blood (hematocrit 41.0 +/- 1.0%). After circulation and collection of baseline samples, the first (low) dose of 4 mg (4000 mcg) of Diprivan 1% was added to the perfusate, followed by the second (high) dose of 40 mg (40,000 mcg) and the final challenge (extreme dose) of 356 mg (356,000 mcg) of Diprivan. Drug assay was done by an independent laboratory, using the standardized method of High Performance Liquid Chromatography (HPLC). Measurements of total propofol were done at baseline, 20 minutes, 40 minutes and 60 minutes after each injection. Oxygenator performance was also measured prior to the addition of propofol and repeated after exposure to 4 mg, 40mg and 356 mg propofol for 60 min, 120 min and 180 minutes of circulation. Results indicate that phosphorylcholine coating does not prevent the adsorption of propofol during extracorporeal circulation and the oxygenator's gas exchange ability is not affected by prolonged exposure to an extreme dose of the medication during high flow extracorporeal circulation.

Post-arterial filter gaseous microemboli activity of five integral cardiotomy reservoirs during venting: an in vitro study.

During a previously published study on gaseous microemboli (GMEs) and perfusionist interventions, it was noted that emboli could be detected after the arterial filter when blood/air challenges entered the membrane oxygenator's integral cardiotomy. The findings indicated that further study into the oxygenator's integral cardiotomy reservoir was warranted. This is the first know published report that connects the vent return to GME activity after the arterial filter. To study the air handling ability of the membranes integral cardiotomy, an in vitro study was conducted on five hard shell coated membrane oxygenators (Terumo Capiox SX25, X coated; Sorin Synthesis, phosphorylcholine coated; Gish Vision, GBS coated; Medtronic Affinity NT, trillium coated; Maquet Quadrox, bioline coated). The oxygenators were matched with their own manufacturer's coated arterial filters (Medtronic 351T Arterial Filter, Sorin Synthesis Integrated Arterial Filter, Terumo CXAF200X Arterial Filter, Gish GAF40GBS-2 Arterial Filter, and Maquet Quart HBF140 Arterial Filter). There were three arms to the study, and three separate oxygenator/filter combinations were used in each arm. The first arm consisted of a pump flow of 4.0 L/min with only the filter purge blood entering the integral cardiotomy. In the second arm, 500 mL/min of simulated vent blood was added to the filter purge blood entering the integral cardiotomy. During the final arm, 200 mL/min of air was added to the vent blood as it entered the integral cardiotomy, to more closely simulate vent return during cardiopulmonary bypass. All GME activity in the oxygenator/filter combinations was examined using the Hatteland CMD20 Microemboli Counter. Placement of the Hatteland probes was 4 in after the hard shell reservoir outlet (PRO) and 12 in after the arterial filter (PAF). When vent blood flow was turned on, there was a significant increase in the PRO microemboli activity detected in all reservoirs. In the PAF position, three of the oxygenator/filter combinations were able to remove 98-99% of the GME, one removed 84.3%, and another removed only 55.5% of the GMEs coming out of the oxygenator's reservoir. All oxygenators were found to have a dramatic increase in reservoir GME activity when the vent was turned on. Depending on the oxygenator/filter combination, vent return into the oxygenator's integral cardiotomy resulted in the presence of significant amounts of GMEs after the arterial filter.

Complications relating to perfusion and extracorporeal circulation associated with the treatment of patients with congenital cardiac disease: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease.

The International Consortium for Evidence-Based Perfusion (www.bestpracticeperfusion.org) is a collaborative partnership of societies of perfusionists, professional medical societies, and interested clinicians, whose aim is to promote the continuous improvement of the delivery of care and outcomes for patients undergoing extracorporeal circulation. Despite the many advances made throughout the history of cardiopulmonary bypass, significant variation in practice and potential for complication remains. To help address this issue, the International Consortium for Evidence-Based Perfusion has joined the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease to develop a list of complications in congenital cardiac surgery related to extracorporeal circulation conducted via cardiopulmonary bypass, extracorporeal membrane oxygenation, or mechanical circulatory support devices, which include ventricular assist devices and intra-aortic balloon pumps. Understanding and defining the complications that may occur related to extracorporeal circulation in congenital patients is requisite for assessing and subsequently improving the care provided to the patients we serve. The aim of this manuscript is to identify and define the myriad of complications directly related to the extracorporeal circulation of congenital patients.

Preventing gaseous microemboli during blood sampling and drug administration: an in vitro investigation.

The detection and prevention of gaseous microemboli (GMEs) during cardiopulmonary bypass has generated considerable interest within the cardiac surgical community. There have been several landmark papers that have used transcranial Doppler devices during cardiopulmonary bypass to detect gaseous microemboli activity in the patients' middle cerebral artery during perfusionist interventions. To determine if this source of emboli could be prevented, a shunt was developed between the oxygenator's sampling manifold and the oxygenator's venous line. This shunt bypassed the venous line and emptied into the oxygenator's integral cardiotomy. An in vitro experiment was performed using three open system oxygenators (Sorin Synthesis, Sorin PrimeOx2, and Terumo Capiox SX25) to compare post-arterial filter emboli detection using the Hatteland CMD20 Microbubble Detector under tightly controlled conditions. After injection of air through the sampling manifold, the PrimeOx2 and the Synthesis oxygenators had statistically significant fewer GMEs with the shunt used than when the shunt was not used. Using a shunt in the sampling manifold during perfusionist interventions will dramatically reduce or eliminate gaseous microemboli transmission to the patient during bypass with both the PrimeOx2 and Synthesis oxygenators. However, results indicate that further study of GME handling with all oxygenator's integral cardiotomies is warranted.

Point of care hematocrit and hemoglobin in cardiac surgery: a review.

The use of point-of-care blood gas analyzers in cardiac surgery has been on the increase over the past decade. The availability of these analyzers in the operating room and post-operative intensive care units eliminates the time delays to transport samples to the main laboratory and reduces the amount of blood sampled to measure such parameters as electrolytes, blood gases, lactates, glucose and hemoglobin/hematocrit. Point-of-care analyzers also lead to faster and more reliable clinical decisions while the patient is still on the heart lung machine. Point-of-care devices were designed to provide safe, appropriate and consistent care of those patients in need of rapid acid/base balance and electrolyte management in the clinical setting. As a result, clinicians rely on their values to make decisions regarding ventilation, acid/base management, transfusion and glucose management. Therefore, accuracy and reliability are an absolute must for these bedside analyzers in both the cardiac operating room and the post-op intensive care units. Clinicians have a choice of two types of technology to measure hemoglobin/hematocrit during bypass, which subsequently determines their patient's level of hemodilution, as well as their transfusion threshold. All modern point-of-care blood gas analyzers measure hematocrit using a technology called conductivity, while other similar devices measure hemoglobin using a technology called co-oximetry. The two methods are analyzed and compared in this review. The literature indicates that using conductivity to measure hematocrit during and after cardiac surgery could produce inaccurate results when hematocrits are less than 30%, and, therefore, result in unnecessary homologous red cell transfusions in some patients. These inaccuracies are influenced by several factors that are common and unique to cardiopulmonary bypass, and will also be reviewed here. It appears that the only accurate, consistent and reliable method to determine hemodilution and establish transfusion thresholds based on nadir hematocrits during cardiopulmonary bypass, and immediately post cardiac surgery, is with the use of co-oximetry.

Clinical evaluation of the Sorin Synthesis oxygenator with integrated arterial filter.

The use of arterial line filters has long been a standard of practice in the field of cardiopulmonary bypass. Sorin Biomedica has designed an adult hollow-fiber oxygenator that not only incorporates their Mimesys biomimicry coating technology but also has a 40-micron arterial filter as an integrated component of this unique membrane oxygenator. We did a prospective, randomized clinical trial of 54 Synthesis coated oxygenators and compared them with 54 uncoated Monolyth Pro oxygenators, the latter of which incorporated an external arterial line filter with a standard bypass loop There were few statistically significant differences found between the Synthesis group and the Monolyth group with regard to pressure differentials, hemodynamic resistance, and platelet drop. The Synthesis oxygenator did require less priming volume, but the amount was not significant. Platelet counts with the Phosphorylcholine coated Synthesis oxygenators, using crystalloid perfusates, was similar to our previously published data on platelet protection and Albumin perfusates. We conclude that the Sorin Synthesis oxygenator appears to have better flow characteristics than the Monolyth oxygenator, with the potential for lower priming volumes. The most clinically significant benefit comes from the elimination of the arterial filter bypass loop and the avoidance of inverting the arterial filter during priming.

A multicenter investigation into the occurrence of high-pressure excursions.

The occurrence of sudden increases in premembrane pressures and membrane pressure differentials has drawn considerable attention and debate in the perfusion community. Several terms have been applied to this phenomenon, but the term that best describes this event is "high-pressure excursion" (HPE). The exact causes of HPE are still uncertain, but nonetheless widely speculated. However, their increased appearance seems to be very closely related to the removal/absence of human serum albumin from priming solutions. To investigate the reasons why HPE occur in some cardiopulmonary bypass cases, we present our findings in a multicenter, retrospective analysis of 2696 cardiopulmonary bypass cases. Of the 31 cases of HPE that were documented from the analysis, 60 preoperative and perioperative variables were gathered from the participating tertiary care centers. Our findings indicate that these pressure excursions had an occurrence of 1.14% in the three centers involved with this analysis. The largest occurrence of HPE tended to be in male (87.1%) coronary artery disease patients (96.8%) during the presence of the IV anesthetic Diprivan (74.2%). In conclusions, HPE are not perfusate related because it occurred in the presence of three perfusate combinations. They also do not seem to be oxygenator related or exclusive to hypothermic temperatures or heat exchangers.

Evaluation of Mimesys phosphorylcholine (PC)-coated oxygenators during cardiopulmonary bypass in adults.

A new generation of coating extracorporeal circuitry with biocompatible polymers has entered the North American perfusion market. This new biomimetic coating process uses synthetic phosphorylcholine (PC) containing polymers to bond covalently to the surface of the Sorin Monolyth oxygenator, under the brand name of Mimesys. In part one of a three-part investigation, 160 Mimesys-coated oxygenators were randomly evaluated against 36 uncoated oxygenators for blood flow, hemodynamic resistance, and pressure differentials. In part two, retrospective analysis of platelet data collected in this study was compared with platelet data collected from a previous investigation using uncoated Monolyth oxygenators with albumin and crystalloid perfusates. Part three examined the risk-adjusted clinical outcomes of 71 patients treated with Mimesys-coated oxygenators, compared with 71 case-matched patients treated with uncoated oxygenators. There was no difference found in the Mimesys-coated group, when compared to the control group, with regard to pressure differentials or hemodynamic resistance. However, we conclude that platelet protection with PC-coated Monolyth's using crystalloid perfusates, was similar to platelet protection with albumin perfusates, and significantly better than uncoated Monolyths using crystalloid perfusates.