First report of the point-of-care TEG: A technical validation study of the TEG-6S system.

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 P2Y12 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.

Characterizing the epidemiology of perioperative transfusion-associated circulatory overload.

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.

Prescriptive patient extracorporeal circuit and oxygenator sizing reduces hemodilution and allogeneic blood product transfusion during adult cardiac surgery.

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.

Computerized bar code-based blood identification systems and near-miss transfusion episodes and transfusion errors.

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.

Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not.

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.

Inhaled carbon monoxide attenuates myocardial inflammatory cytokine expression in a rat model of cardiopulmonary bypass.

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.

Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves.

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.

A prospective, randomized, double-blind trial of 3 regimens for sedation and analgesia after cardiac surgery.

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.

Microporous Polysaccharide Hemospheres do not enhance abdominal infection in a rat model compared with gelatin matrix.

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.

Choice of hemostatic agent influences adhesion formation in a rat cecal adhesion model.

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.

Comparative safety and efficacy of topical hemostatic agents in a rat neurosurgical model.

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.

Renal injury and the application of polysaccharide hemospheres: a laparoscopic experimental model.

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.

Microporous polysaccharide hemospheres for management of laparoscopic trocar injury to the spleen.

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.

A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta.

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.

A prospective, randomized platelet-function study of heparinized oxygenators and cardiotomy suction.

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.

Can the kidney function as a lung? Systemic oxygenation and renal preservation during retrograde perfusion of the ischaemic kidney in rabbits.

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.

Can N-acetylcysteine reverse the antiplatelet effects of clopidogrel? An in vivo and vitro study.

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.

Thirty-day mortality following hip arthroplasty for acute fracture.

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.

Hemofiltration but not steroids results in earlier tracheal extubation following cardiopulmonary bypass: a prospective, randomized double-blind trial.

BACKGROUND: Activation of the inflammatory cascade is thought to account for some of the respiratory dysfunction and prolonged mechanical ventilation associated with cardiopulmonary bypass. The objective of this investigation was to identify whether perioperative steroids or hemofiltration during cardiopulmonary bypass, by their attenuation of inflammation, would reduce duration of mechanical ventilation after cardiac surgery. METHODS: After Institutional Review Board approval and informed consent, 192 patients scheduled to undergo elective primary coronary artery bypass grafting or valvular replacement or repair were randomized in a double-blind prospective study into three groups. One group (Control) received saline at induction and at 6-h intervals for four doses. Another group (Hemofil) received saline and hemofiltration to obtain 27 ml/kg of hemofiltrate. The final group (Steroid) received 1 g methylprednisolone before anesthesia induction and then 4 mg of dexamethasone at 6-h intervals for four doses. All patients underwent normothermic cardiopulmonary bypass and received propofol for postoperative sedation. Separate two-sample comparisons were performed to compare each experimental group versus the control group using the Wilcoxon rank sum test for continuous variables and Fisher exact test for categorical variables. In all cases, two-tailed P values

Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery.

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.