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Background: Hip fractures are associated with a substantial mortality rate. Previous reports on perioperative mortality associated with hip arthroplasty for the treatment of acute fracture have not documented demographic and surgical characteristics that increase the likelihood of death. The purpose of the present study was to determine the prevalence of, and associated risk factors for, perioperative death following hip arthroplasty for the treatment of acute fracture.Methods: Data were compiled from the computerized total joint registry at a single institution to determine the mortality rate following hip arthroplasty according to age, gender, diagnosis, implant type, and fixation mode. A review of this database revealed that 7774 consecutive patients had undergone hip arthroplasty for the treatment of an acute fracture between 1969 and 1997. The medical records of all patients who had died within thirty days after hip arthroplasty were reviewed retrospectively.Results: The overall mortality rate within thirty days after hip arthroplasty for the treatment of an acute fracture was 2.4% (186 of 7774), yet notable variations in the mortality rate were seen within clinical subgroups. The thirty-day mortality rate was significantly higher for patients who had received a cemented implant, female patients, elderly patients, patients with cardiorespiratory comorbidities, and patients with intertrochanteric fractures. With the numbers available, there was no significant difference in mortality between patients who had been managed with total hip arthroplasty and those who had been managed with hemiarthroplasty.Conclusions: Hip arthroplasty for the diagnosis of acute fracture is associated with a nearly tenfold higher rate of perioperative mortality compared with elective hip arthroplasty. Medical optimization, appropriate choice of implants, and vigilant intraoperative management of these patients are essential. [ABSTRACT FROM AUTHOR]

Background: Previous reports on perioperative mortality associated with hip arthroplasty have not documented, to our knowledge, patient characteristics and surgical factors that increase the likelihood of death. The purpose of this study was to determine the prevalence of and associated risk factors for perioperative death after elective hip arthroplasty.Methods: The records of 30,714 consecutive patients who had undergone elective hip arthroplasty at our institution from 1969 to 1997 were retrospectively reviewed to identify patients who had died within thirty days after the procedure. Mortality rates were determined according to age, gender, diagnosis, implant type, and fixation mode.Results: Ninety deaths occurred within thirty days after elective total hip arthroplasty, for an overall mortality rate of 0.29% (ninety of 30,714). The thirty-day mortality rate was significantly higher for patients with preexisting cardiovascular disease (p < 0.0001), male patients (p < 0.0001), and patients who were seventy years of age or older (p < 0.0002). The mortality rate was slightly, but not significantly, higher for patients with an underlying diagnosis of rheumatoid arthritis (p < 0.36) and those receiving cemented implants (p < 0.57). There was no difference in the thirty-day mortality rate for revision as compared with primary hip arthroplasty (p < 0.92).Conclusions: Factors that are associated with an increased risk of mortality within thirty days after elective hip arthroplasty include an older age, male gender, and a history of cardiorespiratory disease. There has been a significant decline in the thirty-day mortality rate after elective hip arthroplasty in the last decade (p < 0.0002); during the 1990s, the overall rate at our institution was 0.15% (twenty-three of 14,989). [ABSTRACT FROM AUTHOR]

Background: The real-world impact of breathing zone air purification and coronavirus disease 2019 (COVID-19) mitigation measures on healthcare-associated infections is not well documented. Engineering solutions to treat airborne transmission of disease may yield results in controlled test chambers or single rooms, but have not been reported on hospital-wide applications, and the impact of COVID-19 mitigation measures on healthcare-associated infection rates is unknown., Aim: To determine the impact of hospital-wide bioaerosol treatment and COVID-19 mitigation measures on clinical outcomes., Methods: The impact of the step-wise addition of air disinfection technology and COVID-19 mitigation measures to standard multi-modal infection control on particle counts, viral and bacterial bioburden, and healthcare-associated infection rates was investigated in a 124-bed hospital (>100,000 patient-days over 30 months)., Findings and Conclusion: The addition of air disinfection technology and COVID-19 mitigation measures reduced airborne ultrafine particles, altered hospital bioburden, and reduced healthcare-associated infections from 11.9 to 6.6 (per 1000 patient-days) and from 6.6 to 1.0 (per 1000 patient-days), respectively (P<0.0001, R 2 =0.86). No single technology, tool or procedure will eliminate healthcare-associated infections, but the addition of a ubiquitous facility-wide engineering solution at limited expense and with no alteration to patient, visitor or staff traffic or workflow patterns reduced infections by 45%. A similar impact was documented with the addition of comprehensive, restrictive, and labour- and material-intensive COVID-19 mitigation measures. To the authors' knowledge, this is the first direct comparison between traditional infection control, an engineering solution and COVID-19 mitigation measures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Controlling indoor air quality and the airborne transmission of infectious agents in hospitals is critical. The most hazardous particles and pathogens are not easily eliminated by traditionally passive air cleansing., Methods: We studied the effect of a novel particle control technology on airborne particulate matter in 2 live real-world operating room settings and on pathogen survival in a microbiology laboratory., Results: Particle control technology reduced operating room particle and pathogen loads by 94.4% in a community hospital operating room, and by 95% in an academic medical center operating room. The addition of particle control technology to a collector loaded with a biologic warfare surrogate resulted in a 95% kill rate of an anthrax surrogate (Bacillus subtilis) within 3 hours., Discussion: Deployment of this emerging technology could significantly reduce indoor air contamination and associated infections in operating rooms, hospital isolation rooms, and intensive care settings, as well as reduce inflammatory responses to airborne particles., Conclusions: The particle control technology studied may protect patients from hospital-acquired infections, reduce inflammatory pulmonary disease, and mitigate exposure to biologic weapons., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Thrombelastography (TEG) measured by the TEG5000 Hemostasis Analyzer is an established but the labor-intensive method for assessing global hemostasis. The first true point-of-care TEG, the TEG6s system, uses resonance-frequency viscoelasticity measurements and a disposable multi-channel microfluidic cartridge to assess hemostasis and response to antiplatelet therapy. TEG assays (n = 5,100) were performed on the blood of healthy volunteers (n = 157) and patients undergoing coronary revascularization at three hospitals (n = 300). The results from the TEG6s were compared with the conventional TEG5000 in accordance with Clinical and Laboratory Standards Institute (CLSI) and FDA recommendations. Precision testing was conducted using blood from healthy donors, all assays were run for 5 consecutive days in duplicate using multiple operators, lots, and instruments. Reference ranges were comparable between the TEG systems. Deming regression analysis demonstrated a strong correlation between the two systems for the standard hemostasis tests (R r = 0.932, MA r = 0.972, LY30 r = 0.938). Method comparison analysis showed an acceptable agreement between PlateletMapping (PM) assays for measuring arachidonic acid (indicator of aspirin response)- and adenosine diphosphate (indicator of P2Y 12 inhibitor response)-induced platelet aggregation (total agreement = 90%, and 72%, respectively). TEG6s precision testing yielded low variability (CV 0-13%) in all measures. The new point-of-care TEG6s is associated with greater ease of use than the TEG5000 and provides precise results. The results correlated between methods for all variables. TEG6s is a promising device for near-patient hemostasis monitoring and future trials of personalized therapy designed to reduce bleeding and thrombosis.

Excessive bleeding and allogeneic transfusion during adult post-cardiotomy venoarterial extracorporeal membrane oxygenation (ECMO) are potentially harmful and expensive. Balancing the inhibition of clotting and distinguishing surgical from non-surgical bleeding in post-operative period is difficult. The sensitivity of coagulation tests including Thromboelastography(®) (TEG) to predict chest tube drainage in the early hours of ECMO was examined with the use of receiver-operating characteristics (ROC). The results are useful to incorporate in clinical evidence-based algorithms to guide management decisions. In the eighth hour of ECMO, 26 of the 53 adult patients (49%) studied were identified as non-bleeders (less than 2.0 mL/kg/h). All had experienced various types of cardiac surgical procedures. Fifty-two percent were female and the group was 54 ± 19 (mean ± 1 SD) years old. The coagulation parameter threshold with the maximum sensitivity and specificity to predict non-bleeding at 8 hours on ECMO was the kaolin plus heparinase TEG maximum amplitude (KH-TEG MA) at a significant ROC threshold (t) > 50 mm. The activated partial thromboplastin time (aPTT) t < 49 seconds, KH-TEG alpha-angle t > 51°, and the kaolin activated clotting time (ACT) t < 148 seconds were sensitive predictors of non-bleeders. The whole-blood KH-TEG MA was superior to the plasma-based aPTT or International Normalization Ratio (INR) to predict bleeding in the eighth hour of ECMO. Using coagulation laboratory thresholds that predict non-bleeding can begin a process of identifying patients earlier that are likely to bleed. Awareness of these parameter thresholds may improve care through patient protection from unnecessary transfusion and prolonging the life of the ECMO circuit. An algorithm incorporating the ROC thresholds was created to help recognize surgical bleeding to minimize unnecessary transfusions.

Background: Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related fatalities, but its incidence and associated patient and transfusion characteristics are poorly understood. To inform surgical transfusion practice and to begin mitigating perioperative TACO, the authors aimed to define its epidemiology., Methods: In this retrospective cohort study, the medical records of adult patients undergoing noncardiac surgery with general anesthesia during 2004 or 2011 and receiving intraoperative transfusions were screened using an electronic algorithm for identification of TACO. Those patients who were screened as high probability for TACO underwent rigorous manual review. Univariate and multivariate analyses evaluated associations between patient and transfusion characteristics with TACO rates in a before-and-after study design., Results: A total of 2,162 and 1,908 patients met study criteria for 2004 and 2011, respectively. The incidence of TACO was 5.5% (119 of 2,162) in 2004 versus 3.0% (57 of 1,908) in 2011 (P < 0.001), with comparable rates for men (4.8% [98 of 2,023]) and women (3.8% [78 of 2,047]) (P = 0.09). Overall, vascular (12.1% [60 of 497]), transplant (8.8% [17 of 193]), and thoracic surgeries (7.2% [10 of 138]) carried the highest TACO rates. Obstetric and gynecologic patients had the lowest rate (1.4% [4 of 295]). The incidence of TACO increased with volume transfused, advancing age, and total intraoperative fluid balance (all P < 0.001)., Conclusions: The incidence of perioperative TACO is similar to previous estimates in nonsurgical populations. There was a reduction in TACO rate between 2004 and 2011, with incidence patterns remaining comparable in subgroup analyses. Future efforts exploring risk factors for TACO may guide preventive or therapeutic interventions, helping to further mitigate this transfusion complication.

Unlabelled: The goal of this cardiopulmonary bypass (CPB) quality improvement initiative was to maximize hemoglobin nadir concentration by minimizing hemodilution and, in turn, eliminating allogeneic blood product transfusion. The effects of transitioning from "one-size-fits-all" to "right-sized" oxygenators, reservoirs, and arterial-venous tubing loops were evaluated through a 2-year retrospective review of 3852 patient perfusion records. Using a sizing algorithm, derived from manufacturers' recommendations, we were able to create individualized "right-sized" extracorporeal circuits based on patient body surface area, cardiac index, and target blood flows. Use of this algorithm led to an increase in the percent of algorithm-recommended smaller oxygenators being used from 39% to 63% (p < .01) and an increase in average hemoglobin nadir from 8.38 to 8.76 g/dL (p < .01). Decreased priming volumes led to increased hemoglobin nadir and decreases in allogeneic blood transfusion (p = .048). Patients with similar body surface areas who previously were exposed to larger oxygenators, reservoirs, and arterial-venous loops were now supported with smaller circuits as a result of the use of the right-sized algorithm. Adjustments to the algorithm were made for unique patients and procedural situations including age, gender, and length and type of procedure. Larger heat exchanger surface area oxygenators were used for circulatory arrest procedures as a result of the need for increased heat exchange capability. Despite the generally higher costs of smaller circuits, reduced transfusion-related expenditures and decreased exposure risks justify the use of smaller circuit components. This quality improvement initiative demonstrated that as an integral part of a multidisciplinary, multimodal blood conservation effort, the use of the "right-sized" circuit algorithm can help to elevate hemoglobin nadir during CPB and eliminate allogeneic blood transfusions to patients undergoing CPB., Keywords: cardiopulmonary bypass, oxygenator, perfusion index, extracorporeal circuit, hemodilution.

Objective: To determine whether the use of a computerized bar code-based blood identification system resulted in a reduction in transfusion errors or near-miss transfusion episodes., Patients and Methods: Our institution instituted a computerized bar code-based blood identification system in October 2006. After institutional review board approval, we performed a retrospective study of transfusion errors from January 1, 2002, through December 31, 2005, and from January 1, 2007, through December 31, 2010., Results: A total of 388,837 U were transfused during the 2002-2005 period. There were 6 misidentification episodes of a blood product being transfused to the wrong patient during that period (incidence of 1 in 64,806 U or 1.5 per 100,000 transfusions; 95% CI, 0.6-3.3 per 100,000 transfusions). There was 1 reported near-miss transfusion episode (incidence of 0.3 per 100,000 transfusions; 95% CI, <0.1-1.4 per 100,000 transfusions). A total of 304,136 U were transfused during the 2007-2010 period. There was 1 misidentification episode of a blood product transfused to the wrong patient during that period when the blood bag and patient's armband were scanned after starting to transfuse the unit (incidence of 1 in 304,136 U or 0.3 per 100,000 transfusions; 95% CI, <0.1-1.8 per 100,000 transfusions; P=.14). There were 34 reported near-miss transfusion errors (incidence of 11.2 per 100,000 transfusions; 95% CI, 7.7-15.6 per 100,000 transfusions; P<.001)., Conclusion: Institution of a computerized bar code-based blood identification system was associated with a large increase in discovered near-miss events., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Major trauma is an independent risk factor for developing venous thromboembolism. While increases in thrombin generation and/or procoagulant microparticles have been detected in other patient groups at greater risk for venous thromboembolism, such as cancer or coronary artery disease, this association has yet to be documented in trauma patients. This pilot study was designed to characterize and quantify thrombin generation and plasma microparticles in individuals early after traumatic injury., Methods: Blood was collected in the trauma bay from 52 blunt injured patients (cases) and 19 uninjured outpatients (controls) and processed to platelet poor plasma to allow for (1) isolation of microparticles for identification and quantification by flow cytometry, and (2) in vitro thrombin generation as measured by calibrated automatic thrombography. Data collected are expressed as either mean ± standard deviation or median with interquartile range., Results: Among the cases, which included 39 men and 13 women (age, 40 ± 17 years), the injury severity score was 13 ± 11, the international normalized ratio was 1.0 ± 0.1, the thromboplastin time was 25 ± 3 seconds, and platelet count was 238 ± 62 (thousands). The numbers of total (cell type not specified) procoagulant microparticles, as measured by Annexin V staining, were increased compared to nontrauma controls (541 ± 139/μL and 155 ± 148/μL, respectively; P < .001). There was no significant difference in the amount of thrombin generated in trauma patients compared to controls; however, peak thrombin was correlated to injury severity (Spearman correlation coefficient R, 0.35; P = .02)., Conclusion: Patients with blunt trauma have greater numbers of circulating procoagulant microparticles and increased in vitro thrombin generation. Future studies to characterize the cell-specific profiles of microparticles and changes in thrombin generation kinetics after traumatic injury will determine whether microparticles contribute to the hypercoagulable state observed after injury., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Hibernating mammals have developed many physiological adaptations to extreme environments. During hibernation, 13-lined ground squirrels (Ictidomys tridecemlineatus) must suppress hemostasis to survive prolonged body temperatures of 4-8°C and 3-5 heartbeats per minute without forming lethal clots. Upon arousal in the spring, these ground squirrels must be able to quickly restore normal clotting activity to avoid bleeding. Here we show that ground squirrel platelets stored in vivo at 4-8°C were released back into the blood within 2 h of arousal in the spring with a body temperature of 37°C but were not rapidly cleared from circulation. These released platelets were capable of forming stable clots and remained in circulation for at least 2 days before newly synthesized platelets were detected. Transfusion of autologous platelets stored at 4°C or 37°C showed the same clearance rates in ground squirrels, whereas rat platelets stored in the cold had a 140-fold increase in clearance rate. Our results demonstrate that ground squirrel platelets appear to be resistant to the platelet cold storage lesions observed in other mammals, allowing prolonged storage in cold stasis and preventing rapid clearance upon spring arousal. Elucidating these adaptations could lead to the development of methods to store human platelets in the cold, extending their shelf life.

We studied the ability of a new instrument, the PlaCor PRT that measures shear-induced platelet aggregation in fingerstick, non-anticoagulated blood without added agonists, to detect platelet dysfunction ex vivo. Platelet reactivity time (PRT) and whole blood aggregation (WBA) were measured in 160 healthy volunteers, before and after aspirin and in 170 participants with established vascular disease or risk factors thereof treated with aspirin ± clopidogrel. Pretreatment PRT and WBA were significantly correlated (collagen r = -.63; arachidonate r = -.65; P < .0001). Following aspirin, the mean PRT increased from 82 to 142 seconds (P < .0001), and in participants treated with clopidogrel-aspirin, the mean PRT (286 seconds, n = 65) was significantly longer than with aspirin alone (166 seconds, n = 105; P < .001). Only 13% of PRTs of participants treated with clopidogrel and aspirin were within the normal range. We conclude that the PlaCor PRT is a simple, rapid, point-of-care instrument that compares favorably with published descriptions of other platelet function instruments.

Carbon monoxide (CO), a by-product of Heme metabolism, is a potent modulator of inflammation. Low dose inhaled CO has demonstrated reduced lung and kidney injury in animal models of cardiopulmonary bypass (CPB). We evaluated the impact of low dose inhaled CO on systemic, pulmonary, and myocardial inflammatory response to CPB in rats. Sixteen male Sprague-Dawley rats underwent CPB for 1 hour. The CO (n = 8) group received inhaled CO at 250 ppm for 3 hours before CPB. The Air (n = 8) group served as the control. Pulmonary mechanics were assessed pre and post CPB. The animals were recovered for 30 minutes post CPB and subsequently sacrificed. Pre CPB and post CPB serum Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-10 (IL-10) were analyzed by enzyme-linked immunosorbent assay. Gene expression array and real time quantitative polymerase chain reaction (PCR) analysis was performed on the extracted heart tissue. Baseline characteristics were similar between the groups with the expected exception of carboxyhemoglobin levels (p < or = .001) and oxyhemoglobin saturation (p < or = .01) in Air versus CO treated groups, respectively. Serum TNF-alpha (363 +/- 278 vs. 287 +/- 195;p = .13) and IL-10 (237 +/- 26 vs. 302 +/- 137; p = Not Significant) in Air versus CO groups respectively were not statistically different after CPB, despite showing a trend of inflammatory attenuation. Gene expression array of the myocardial tissue suggested a pattern of inflammatory modulation, which was confirmed by real time quantitative PCR demonstrating IL-10 expression 3.13 times higher (p = .02) in the CO treated group compared to the Air group. These data demonstrate that pretreatment with CO at 250 ppm may have a modulatory effect on the inflammatory response to CPB without compromising hemodynamics or oxygen delivery. Further investigation in a survival model of CPB is warranted.

Objective: Warfarin reduces risk of stroke in patients with mechanical heart valves but increases risk of hemorrhage and is difficult to use. Dabigatran etexilate, a new oral direct thrombin inhibitor, is safe and effective in reducing risk of stroke among patients with atrial fibrillation. No data exist in the setting of mechanical heart valves. We tested the hypothesis that dabigatran etexilate is as effective as heparin for thromboprophylaxis of mechanical valves in a porcine heterotopic aortic valve model., Methods: Thirty swine underwent implantation of modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals randomly received no anticoagulation (n = 10), enoxaparin 2 mg/kg subcutaneously twice daily (n = 10), or dabigatran etexilate 20 mg/kg orally twice daily. Primary end point was amount of valve thrombus at 30 days. Secondary end points included quantitative measurement of platelet deposition on valve prosthesis, thromboelastography, and hemorrhagic and embolic events., Results: At 30 days, we observed 638 ± 895 mg thrombus in no anticoagulation group, 121 ± 128 mg in enoxaparin group, and 19 ± 31 mg in dabigatran etexilate group (P = .01 enoxaparin vs dabigatran etexilate). Fewer platelets were deposited on valves in dabigatran etexilate group (2.7 × 10(8)) than in enoxaparin group (1.8 × 10(9), P = .03). No major or occult hemorrhagic or embolic events were observed. By thromboelastographic analysis, dabigatran etexilate produced less prolongation of K value (P = .01) and less decreases in angle (P = .01) and maximum amplitude (P = .001) than enoxaparin., Conclusions: Dabigatran etexilate is as effective as enoxaparin for short-term thromboprophylaxis of mechanical valves. It prevents valve thrombus and platelet deposition at 30 days without increased adverse events. These promising results serve as a foundation for prospective clinical trials with dabigatran etexilate as an alternative to warfarin in patients with bileaflet mechanical aortic valves., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The aim of this study was to evaluate cardiac risk as a consideration for selecting postoperative sedation and analgesia regimens used for cardiac surgical patients requiring cardiopulmonary bypass and early extubation., Design: An observer-blind, randomized, controlled trial., Setting: A tertiary referral medical center involving an intensive care unit., Participants: One hundred forty-five adults requiring elective cardiac surgery., Interventions: Patients were stratified preoperatively as low, moderate, or high cardiac risk based on established criteria and then assigned to 1 of 3 postoperative regimens: propofol infusion beginning at 25 μg/kg/min and morphine boluses (P), fentanyl infusion beginning at 2 μg/kg/h and midazolam boluses (F), or propofol and fentanyl infusions beginning at 25 μg/kg/min and 0.5 μg/kg/h (PF), respectively., Measurements and Main Results: Postoperative regimen P was associated with a significantly reduced time to extubation (median value, 264 minutes; p = 0.05) compared with F (295 minutes) but not PF (278 minutes) in patients characterized as low cardiac risk. The time to extubation did not differ among regimens in patients of moderate/high cardiac risk., Conclusion: Patients with low cardiac risk undergoing cardiac surgery had statistically significantly shorter times to extubation with propofol infusion and intermittent morphine than a fentanyl infusion and intermittent midazolam. These differences were not sustained in patients considered at higher cardiac risk. The time to extubation after cardiac surgery may further improve if postoperative sedation and analgesia are not administered uniformly to all patients but selected based on individual characteristics., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cardiopulmonary bypass (CPB) is associated with significant postoperative morbidity, but its effects on the neuromuscular system are unclear. Recent studies indicate that even relatively short periods of mechanical ventilation result in significant neuromuscular effects. Carbon monoxide (CO) has gained recent attention as therapy to reduce the deleterious effects of CPB. We hypothesized that 1) CPB results in impaired neuromuscular transmission and reduced diaphragm force generation; and 2) CO treatment during CPB will mitigate these effects. In adult male Sprague-Dawley rats, diaphragm muscle-specific force and neuromuscular transmission properties were measured 90 min after weaning from normothermic CPB (1 h). During CPB, either low-dose inhaled CO (250 ppm) or air was administered. The short period of mechanical ventilation used in the present study ( approximately 3 h) did not adversely affect diaphragm muscle contractile properties or neuromuscular transmission. CPB elicited a significant decrease in isometric diaphragm muscle-specific force compared with time-matched, mechanically ventilated rats ( approximately 25% decline in both twitch and tetanic force). Diaphragm muscle fatigability to 40-Hz repetitive stimulation did not change significantly. Neuromuscular transmission failure during repetitive activation was 60 +/- 2% in CPB animals compared with 76 +/- 4% in mechanically ventilated rats (P < 0.05). CO treatment during CPB abrogated the neuromuscular effects of CPB, such that diaphragm isometric twitch force and neuromuscular transmission were no longer significantly different from mechanically ventilated rats. Thus, CPB has important detrimental effects on diaphragm muscle contractility and neuromuscular transmission that are largely mitigated by CO treatment. Further studies are needed to ascertain the underlying mechanisms of CPB-induced neuromuscular dysfunction and to establish the potential role of CO therapy.

Introduction: Hemostatic agents are frequently used during abdominal surgery and some are linked to adhesion formation. We sought to evaluate the impact of several commonly used hemostatic agents on adhesion formation in a rat peritoneal model., Methods: In our study, Wister outbred rats underwent laparotomy and excision of a portion of their peritoneum to initiate adhesion formation process. One of six different hemostatic agents, namely, activated starch microspheres (Arista AH; Medafor Inc., Minneapolis, MN), glutaraldehyde activated collagen (BioGlue; Cryolife Inc., Kennesaw, GA), thrombin coated collagen microspheres (FloSeal; Baxter Inc., Deerfield, IL), thrombin activated fibrin polymer (Tisseel, Baxter), polyethylene glycol polymer (CoSeal, Baxter), or oxidized cellulose (Surgicel; Ethicon Inc., Somerville, NJ), was placed in the area of peritoneal defect. All animals were sacrificed on post-op day 7 and strength and extent of adhesion formation was determined. Histopathological examination of rat caecum was also performed., Results: Arista and CoSeal showed significantly lower adhesion formation than controls (P < 0.05). Higher adhesion scores were seen in BioGlue (P < 0.05) treated rats. Additionally, histopathologic examination showed that BioGlue caused statistically more inflammation and necrosis than controls (P < 0.05). Total adhesion score increased with residual amount of agent present at 7 d., Conclusions: Use of Arista and CoSeal may help in reducing peritoneal adhesions after intra-abdominal surgeries. Furthermore, there appears to be a relationship between the creation of inflammation and necrosis in tissues and the eventual formation of adhesions. This could aid in improving the design of these agents in the future.

Background: Residual topical hemostatic material can serve as a nidus for infection or enhance infection in an already contaminated wound. A newly approved agent, Microporous Polysaccharide Hemospheres (MPH) (Arista AH), has rapid degradation properties, which may reduce the chance of surgical site infection., Materials and Methods: With institutional approval, 170 Wister rats underwent standardized anesthesia and abdominal surgery. An Echerichia coli inoculum was added to the incision, and MPH, gelatin matrix, or no agent (control) was placed in the site. After 72 h, the animals were sacrificed, and colony-forming units (cfu)/g were counted in the harvested tissue., Results: Application of gelatin matrix resulted in more cfu/g of tissue and an 87% infection rate, with fewer cfu/g of tissue and a 14% and 24% infection rate in the control and MPH groups, respectively., Conclusion: The use of MPH in this rat abdominal infection model did not enhance infection. Gelatin matrix was associated with a greater infection rate than MPH. The rapid degradation of MPH may account for these results, making it a good hemostat in the presence of infective sources.

Objective: Adequate hemostasis is extremely important in neurosurgery, commonly requiring the use of topical hemostatic agents. Apart from variable efficacy, the residual presence of these agents may cause foreign body reaction, infection, and delayed bone growth. This study compares the safety and efficacy of commonly used agents with a newly approved agent, Arista (microporous polysaccharide hemospheres; Medafor, Inc., Minneapolis, MN)., Methods: A brain tissue defect was created in 228 Wistar outbred rats, and either no agent (negative control), Arista, Surgicel (oxidized cellulose; Ethicon, Inc., Somerville, NJ), Avitene (microfibrillar collagen; Alcon, Inc., Humacao, PR), FloSeal (gelatin matrix thrombin sealant; Baxter Healthcare Corp., Deerfield, IL), or kaolin (positive control) was implanted. Time to hemostasis was documented. The animals were sacrificed at different intervals up to 28 days, and presence of residual material and foreign body reaction was determined., Results: Arista, Avitene, FloSeal, and Surgicel performed better (defined as complete hemostasis within 1 minute) than control (no treatment). Residual material was not present at any time with Arista, markedly contrasting with the presence of residual material in 100% of lesions in the Avitene, FloSeal, and Surgicel groups on Day 14. Avitene and FloSeal also demonstrated a propensity for causing granuloma formation, whereas Arista and Surgicel showed no such evidence., Conclusion: Each of these hemostatic agents was effective in controlling bleeding in the majority of standardized neurosurgical lesions. Arista degrades more rapidly than Surgicel, Avitene, and FloSeal and does not result in any foreign body reaction.

Background and Purpose: Microporous polysaccharide hemospheres (MPH) are hemostatic beads engineered from purified plant starch. MPH accelerates the natural clotting cascade by concentrating clotting factors and proteins on their surface while absorbing aqueous and low molecular weight components from blood. The purpose of this study was to determine the efficacy of MPH in achieving hemostasis in the setting of laparoscopic renal injury., Materials and Methods: In four domestic pigs, 16 laparoscopic renal trocar injuries were created (8 each of 12 and 5 mm). A standard hand-assisted laparoscopic approach was used to each kidney so that two lesions per kidney were randomly created. MPH was applied to each treatment lesion with light pressure maintained for 60 seconds. Four of the 16 lesions, two each of 12 and 5 mm, were allowed to bleed as controls. Hemostasis was defined as no active bleeding or oozing. The animals were sacrificed at the conclusion of the procedure., Results: The mean time to hemostasis for the 12-mm MPH and control lesions was 196.2 +/- 53.3 and 372.0 +/- 225.6 seconds, while the average blood loss was 8.3 +/- 3.7 and 12.0 +/- 4.9 g, respectively. For the 5-mm MPH and control lesions, the average time to hemostasis was 100.2 +/- 24.8 and 247.0 +/- 134.4 seconds, while the average blood loss was 8.3 +/- 3.8 and 9.0 +/- 0.7 g, respectively. The median number of applications of the MPH for the 5- and 12-mm injuries was 1 and 2, respectively., Conclusions: MPH provided a rapid and effective means of hemostasis for laparoscopic renal parenchymal injuries in this model. Additional evaluation is warranted, however, before general application is advisable.

Background: Management of iatrogenic injuries during laparoscopy can be arduous. Recent advancements in surgical hemostatic agents have provided beneficial therapeutic alternatives. This project evaluates microporous polysaccharide hemospheres (MPH), with demonstrated efficiency achieving topical hemostasis, in the setting of intracorporeal laparoscopic splenic injury., Methods: Four domestic female pigs were subjected to reproducible laparoscopic 12-mm and 5-mm trocar splenic injuries. Each surgery was an identical transperitoneal hand-assisted laparoscopic procedure. Hemostasis, or no bleeding after treatment, was achieved by measured dose applications of MPH., Results: The MPH successfully achieved hemostasis for all splenic injuries except in 1 case, where a 12-mm lesion transected the splenic artery. The mean time to hemostasis, applications of MPH, and estimated blood loss for the 5- and 12-mm injuries were 165.3 +/- 45.7 and 200.7 +/- 106.5 seconds, 1.3 +/- .5 applications for both, and 12.0 +/- 4.6 and 17.7 +/- 9.1 g, respectively., Conclusions: MPH represents a powerful hemostatic agent that demonstrated complete hemostasis for iatrogenic splenic injury.

Study Objective: To determine whether a new Sonoclot-based, aprotinin-insensitive activated clotting time (aiACT) assay yields stable results over a broad range of aprotinin concentrations., Design: Prospective trial conducted on in vitro blood samples., Setting: Tertiary-care teaching medical center., Participants: 19 healthy adult volunteers., Interventions: Whole blood samples were collected from volunteers. Heparin (2 U/mL) and escalating concentrations of aprotinin of 160 to 500 kallikrein inhibitory units (KIU)/mL were added in vitro., Measurements and Main Results: Celite ACT, kaolin ACT, and aiACT assays were completed. The aiACT showed stable activated clotting time (ACT) results on heparinized, noncitrated blood with added aprotinin (P = nonsignificant). In contrast, celite ACT and kaolin ACT were greatly prolonged when aprotinin was added to heparinized, noncitrated, and citrated blood (P < 0.05). The aiACT had consistent results at all aprotinin concentrations (P = nonsignificant)., Conclusions: Aprotinin (160, 320, and 500 KIU/mL) significantly prolongs the ACT value with celite and kaolin activators but not with the aprotinin-insensitive activator.

Fenoldopam, a selective dopamine-1-receptor agonist, decreases arterial blood pressure rapidly, with a brief duration of action similar to sodium nitroprusside (SNP), but in contrast to SNP, it increases renal blood flow. We compared the hemodynamic and renal effects of fenoldopam in patients undergoing abdominal aortic surgery requiring cross-clamping of the aorta with another therapeutic option, dopamine and SNP. Fenoldopam or 2 mcg x kg(-1) x min(-1) of dopamine and SNP was infused before incision in 60 randomly selected patients in a double-blind fashion. Hemodynamic variables were recorded before incision, immediately before clamping the aorta, 5 min after cross-clamp release and upon completion of surgery. Urine output, serum creatinine, and creatinine clearance were measured intraoperatively and postoperatively. Characteristics were compared between groups using two-sample rank sum test for continuous variables and Fisher's exact test for discrete variables. The occurrence of severe hypotension, maximum systolic blood pressure, and need for additional antihypertensive drugs were not different between the groups. Most intraoperative hemodynamic variables and all indices of renal function did not differ according to treatment. Therefore, fenoldopam has no therapeutic advantage compared with similar therapies in patients undergoing major vascular surgery involving cross-clamping of the aorta.

Objective: To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology., Materials and Methods: After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment., Results: The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC., Conclusion: Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.

Objective: The purpose of this study was to determine if substitution of a heparin-coated oxygenator and salvaged autologous blood for cardiotomy suction would improve platelet function., Design: A prospective, randomized trial., Setting: A large academic medical center., Participants: Sixty adult patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB)., Interventions: Patients were randomized into 1 of 4 groups in a 2 x 2 factorial design by oxygenator (heparinized v nonheparinized) and blood salvage during CPB (cardiotomy suction v salvaged autologous blood)., Measurements and Main Results: Primary outcome measures were platelet function, glass-bead retention, platelet dense-body adenosine triphosphate secretion, platelet-rich plasma (PRP) aggregometry, Plateletworks platelet-function analyzer (Helena Laboratories Corp, Allen Park, MI), and platelet count. Secondary outcome measures were chest-tube drainage and allogeneic blood transfusion requirements. All platelet-function tests except thrombin-receptor activator peptide-induced PRP aggregometry showed a reduction in platelet function during and immediately after CPB (all p < 0.05). The only statistically significant difference in platelet-function tests between the groups was the glass-bead assay at 5 minutes before discontinuation of CPB (p < 0.05). This difference resolved 10 minutes after protamine administration. There were no differences between the groups in the amount of blood transfused, chest-tube drainage, and routine laboratory test results., Conclusions: The authors concluded that the effects of these changes to the CPB circuit were small and inconsequential in this cohort of patients.

Objectives: We evaluated the efficacy of Microporous Polysaccharide Hemospheres (MPH) for parenchymal hemostasis during laparoscopic partial nephrectomy (LPN) in the porcine model., Methods: Six female farm pigs underwent a transperitoneal right lower-pole LPN during occlusion of the renal hilum. Renal parenchyma was excised using cold Endoshears. MPH was applied to the defect and the hilar clamp released. Animals were kept alive for one week. Before sacrifice, left LPN was similarly performed using MPH. Study variables included blood loss, number of MPH applications, hilar clamp time, hemostasis time, perioperative complications, and abnormalities noted at sacrifice., Results: Hemostasis was achieved in all kidneys solely by using MPH. The average excised specimen represented 5.6% (range, 3.6 to 8.5) of renal weight. Mean hilar clamp and hemostatic times were 12.8 minutes (range, 6 to 18) and 2 minutes (range, 1 to 3), respectively. Hemostasis occurred after one MPH application in 8 kidneys (67%). In 3 kidneys, additional MPH powder was required to treat minor residual bleeding. In the remaining kidney, a second standard MPH application was required for hemostasis. No operative complications were encountered. No hematomas or residual MPH was found at necropsy; however, small urinomas were found in 2 of 6 kidneys., Conclusions: In the experimental porcine model, this initial study suggests that MPH provides effective parenchymal hemostasis during laparoscopic resection of an exophytic kidney lesion.

Background: The active metabolite of clopidogrel binds the P2Y12 ADP receptor on the platelet surface via a disulfide bond. N-Acetylcysteine (NAC) is able to reduce disulfide bonds. We postulated that NAC might reverse clopidogrel's effect on platelets., Methods: Two groups of patients were investigated. Group 1 included 11 patients with stable coronary disease who, after discontinuation of aspirin, received 14 days of clopidogrel, 75 mg/day. Bleeding time and whole-blood platelet aggregometry (with 5 micromol/L ADP) were compared before and after the 14 days. Patients were then treated with 6 g of NAC orally, followed by repeat measurement of bleeding time and aggregometry. In group 2, 14 patients were treated with clopidogrel (300 mg) and aspirin before a percutaneous coronary intervention. Blood was drawn 22 +/- 3 hours later and divided into 2 samples. One was sent immediately for platelet-rich plasma aggregometry (using 5 and 2 micromol/L ADP, collagen, and arachidonic acid as agonists), thromboelastography, and aggregometry using the Plateletworks assay (Helena Laboratories, Beaumont, Tex). The other sample was treated with NAC (500 mg/L), after which these same platelet function tests were performed., Results: In group 1, NAC therapy did not significantly change the bleeding time or results of aggregometry. In group 2, neither aggregometry nor the Plateletworks assay suggested reversal of inhibition by NAC., Conclusions: These studies reveal that a large dose of NAC does not reduce inhibition of platelet aggregation by clopidogrel in vitro or in vivo.

Purpose: Microporous polysaccharide hemospheres (MPH, Medafor, Minneapolis, Minneapolis) are a novel hemostatic agent made from purified plant starch. MPH activates the clotting cascade and hyperconcentrates platelets and coagulation proteins, while enhancing a hemostatic plug. We evaluated the hemostatic efficacy of MPH compared with standard surgical technique in a porcine open partial nephrectomy model., Materials and Methods: Standardized lower pole partial nephrectomy was consecutively performed in each kidney of 12 female pigs. Each pig was randomized to 2 groups, namely treatment with MPH application or control with the conventional surgical technique (oxidized cellulose with bolster sutures). The right kidney was harvested 1 half-hour after hemostasis was achieved and the left kidney was harvested after 7 days., Results: Mean animal and resected renal tissue weight were comparable. Ischemic and hemostasis times were significantly decreased in the MPH treated group (2.67 and 4.67 minutes, respectively) vs the control group (8.33 and 7.75 minutes, respectively) (each p = 0.004). Blood loss was equivocal (0.88 gm in the treatment group vs 2.09 gm in the control group, p = 0.07). No hemostatic complications were noted in either group. No evidence of residual foreign material was found in the MPH group at 1 week., Conclusions: MPH provided rapid, effective and durable hemostasis in the porcine open partial nephrectomy model. Additional experimental and clinical evaluation is warranted to define the role of MPH assisted partial nephrectomy in humans.

Objectives: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay., Methods: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU.kg(-1).h(-1) continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (<10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables., Results: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r =.57, P =.003; r =.69, P =.001, respectively)., Conclusion: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.

Background: Infants and children undergoing cardiopulmonary bypass become substantially hemodiluted secondary to the volume used to prime the oxygenator. Fresh-frozen plasma has been included in the prime to lessen dilution of clotting factors and correspondingly minimize blood loss and transfusions., Methods: We prospectively randomized 56 patients weighing 10 kg or less who required cardiopulmonary bypass to receive either one unit of fresh-frozen plasma or 200 mL of albumin 5% in the prime. After protamine administration, samples for prothrombin time, fibrinogen, platelet count, and thromboelastogram were obtained. Mediastinal chest tube drainage and transfusion requirements were documented., Results: There were no significant differences between groups regarding demographic or surgical characteristics. Blood loss during the first 24 hours was similar in both groups, but total transfusions were significantly greater in those who received fresh-frozen plasma instead of albumin 5% in the prime (8.0 +/- 4.2 versus 6.1 +/- 4.5 U, respectively; p = 0.035). Post hoc analyses suggest that for cyanotic patients and patients undergoing complex operations, fresh-frozen plasma in the prime results in less blood loss than albumin 5%., Conclusions: Substitution of albumin 5% for fresh-frozen plasma in the prime of acyanotic patients weighing 10 kg or less who undergo noncomplex operations requiring cardiopulmonary bypass significantly reduces perioperative transfusions without increasing blood loss. Further investigation is needed to determine whether increased blood loss is associated with increased transfusions when albumin 5% is substituted for fresh-frozen plasma in the prime of infants and children who are cyanotic or undergoing complex operations.

Objective: To assess the effect of heparin-coated circuits on bleeding, transfusion, and platelet count in patients undergoing primary coronary artery bypass grafting with full heparinization., Design: Randomized, double-blind study., Setting: Tertiary-care academic medical center., Participants: Eighty-eight patients undergoing coronary artery bypass grafting requiring cardiopulmonary bypass (CPB) without previous sternotomy., Interventions: Subjects received either a heparin-coated or an uncoated extracorporeal circuit for CPB. Heparin, 300 micro/kg, was administered, and supplemental amounts were administered to maintain an activated coagulation time of greater than 480 seconds. Platelet counts were determined during CPB. Mediastinal chest tube drainage was collected in the intensive care unit for 24 hours., Measurements and Main Results: The mean platelet counts were similar between the groups during CPB. There was no significant difference in 24-hour mediastinal chest tube drainage (mean +/- standard deviation; median) between the heparin-coated (n = 44, 1096 +/- 401, 1015 mL) and uncoated group (n = 44, 1150 +/- 548, 1040 mL; p = 0.91). The heparin-coated group received less allogeneic packed red blood cells (0.9 +/- 1.6, 0.0 v 1.5 +/- 1.8, 1.0 U; p = 0.04)., Conclusions: The use of a heparin-coated or uncoated cardiopulmonary bypass circuit and full heparinization marginally reduced only red blood cell transfusion but was not associated with platelet sparing or reduced perioperative bleeding., (Copyright 2003 Elsevier Inc. All rights reserved.)

Unlabelled: Aprotinin is effective during cardiac surgery for reducing blood loss and transfusion requirements, but it is expensive. Aprotinin is usually administered to adults according to a fixed protocol regardless of the patient's weight. We previously developed a weight-based dosing protocol for aprotinin. The purpose of this prospective observational study was to determine aprotinin levels in four patient groups (n = 10 each) using the new weight-based aprotinin dosing schedule that should achieve concentrations over 100, 150, 200, and 250 kallikrein inhibitory units/mL compared with full-dose aprotinin regimen (n = 10) by a simple functional aprotinin assay. There was no difference in patient demographic or surgical variables among groups. There was less within patient variation in plasma aprotinin concentrations over time in the new weight-based aprotinin dosing schedule groups compared with the full-dose aprotinin regimen group (P < 0.02 for all comparisons). The mean plasma aprotinin concentration achieved with the new weight-based aprotinin dosing schedule was similar to the desired concentrations, but we were unable to reduce between-patient variability in aprotinin concentrations., Implications: The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations between patients and a large variation within each patient over time. A new weight-based dosing schedule reduced variation of aprotinin concentration over time, but was unable to reduce between-patient variability in aprotinin concentration.

Objective: To determine if the Trillium Biopassive Surface (Medtronic Cardiopulmonary, Minneapolis, MN) coating added to the cardiopulmonary bypass oxygenator reduces inflammatory mediators, blood loss, and transfusion requirements., Design: Prospective, randomized, and blinded human trial., Setting: Tertiary care academic medical center., Participants: Thirty adult patients undergoing elective coronary artery bypass graft surgery., Interventions: Patients received visually identical coated or uncoated oxygenators., Measurements and Main Results: Hemoglobin, hematocrit, leukocyte count, platelet count, terminal complement complex, complement activation, myeloperoxidase, beta-thromboglobulin, prothrombin fragment 1.2, plasmin-antiplasmin, heparin concentration, activated coagulation time, and fibrinogen concentration were measured. Blood loss and blood product usage were recorded. In both groups, there were significant inflammatory alterations with the initiation of cardiopulmonary bypass. In the postprotamine samples, the coated oxygenator group had small but significant increases in hemoglobin, hematocrit, and leukocyte count. There were no differences in inflammatory mediators, blood loss, or transfusion requirements between the coated and uncoated groups., Conclusion: This human trial of Trillium Biopassive Surface-coated oxygenators did not show clinical benefits or clinically important biochemical results., (Copyright 2001 by W.B. Saunders Company)

The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P =.0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24-hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT.

Background: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding., Methods: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests., Results: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032)., Conclusions: Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.

Unlabelled: Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1) via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/- 16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time x creatinine concentration interaction (P < 0.001)., Implications: A 10 mg/kg initial dose of tranexamic acid followed by an infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The dosing of tranexamic acid may require adjustment for renal insufficiency.

Objective: To determine if the platelet glass bead retention assay can predict bleeding after cardiac surgery., Design: Prospective, observational study., Setting: Large, tertiary care, academic medical center., Participants: Forty-three adult patients scheduled to undergo elective cardiac surgery employing cardiopulmonary bypass (CPB)., Measurements and Main Results: Whole blood samples were observed for platelet count, prothrombin time, and platelet (glass bead) retention assay. The platelet retention and prothrombin times were independent univariant and multivariant predictors of bleeding after CPB (r = 0.554, p = 0.0002 and r = 0.655, p = 0.00001)., Conclusion: The platelet glass bead retention assay measures dynamic platelet function and is sensitive to the CPB-induced adhesion and aggregation defect and correlates with postoperative blood loss. Modification of this platelet function assay used with the prothrombin time may provide a simple and effective diagnostic approach to bleeding after CPB.

Background: Desmopressin (DDAVP) has been evaluated in many randomized clinical trials as a means to reduce blood loss and transfusion of allogeneic blood in cardiac operation requiring cardiopulmonary bypass. Desmopressin reduces blood loss in adult patients with excessive bleeding after cardiac operation. Its usefulness in patients undergoing complex congenital heart repair with cardiopulmonary bypass is unproved., Methods: Sixty patients younger than 40 years of age scheduled for complex congenital heart operation (44 redo, 16 primary) were enrolled in this prospective, randomized, double-blind trial. Desmopressin 0.3 microg/kg or placebo was administered 10 minutes after protamine administration. Transfusion requirements and postoperative blood loss were recorded. Differences were analyzed using analysis of variance with a p value of 0.05 or less used to denote statistical significance., Results: There were no differences in demographic or surgical characteristics between the DDAVP or placebo groups. There was no difference in blood loss and transfusion requirements between the DDAVP and placebo groups. During the intraoperative postinfusion time period, the median blood loss for redo patients was 343 versus 357 mL/m2 for placebo versus DDAVP, respectively, and for primary patients, the median blood loss was 277 versus 228 mL/m2., Conclusions: The prophylactic use of DDAVP to reduce excessive bleeding or transfusion requirements in patients undergoing complex congenital heart operations is not warranted.

Unlabelled: Aprotinin is an effective but expensive drug used during cardiac surgery to reduce blood loss and transfusion requirements. Currently, aprotinin is administered to adults according to a fixed protocol regardless of the patient's weight. The purpose of this study was to determine aprotinin levels in patients receiving full- and half-dose aprotinin regimens by a simple functional aprotinin assay and to design a more individualized aprotinin dosage regimen for cardiac surgical patients. The mean plasma aprotinin concentration peaked 5 min after the initiation of cardiopulmonary bypass (full 401 +/- 92 KIU/mL, half 226 +/- 56 KIU/mL). The mean plasma aprotinin concentration after 60 min on cardiopulmonary bypass was less (full 236 +/- 81 KIU/mL, half 160 +/- 63 KIU/mL). There was large variation in the aprotinin concentration among patients. A statistically significant correlation was found between aprotinin concentration and patient weight (r(2) = 0.67, P < 0.05)., Implications: The current dosing schedule for aprotinin results in a large variation in aprotinin plasma concentrations among patients and a large variation within each patient over time. We combined the information provided by our study with that of a previous pharmacokinetic study to develop a potentially improved, weight-based, dosing regime for aprotinin.

Objective: To determine the blood loss associated with coronary angiography and its impact on hemoglobin and transfusion requirements for subsequent coronary artery bypass graft (CABG) surgery., Design: Retrospective chart review., Setting: Tertiary-care, academic medical center., Participants: A total of 506 adult patients undergoing coronary angiography and CABG surgery., Interventions: None (observational study)., Measurements and Main Results: Coronary angiography was associated with a reduction in hemoglobin of 1.8 g/dL. This reduction in hemoglobin was a significant predictor of allogeneic red blood cell transfusion., Conclusion: Coronary angiography contributes to a 1.8 g/dL reduction in hemoglobin concentration before CABG surgery and was associated with increased transfusion of allogeneic blood products. Measures aimed at maintaining red cell volume during coronary angiography, increasing erythropoiesis, or delaying surgery beyond 2 weeks may result in a decrease in transfusion requirements for patients undergoing CABG surgery.

Background: Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy., Methods: In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group)., Results: There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia., Conclusions: The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.