Colloid Oncotic Pressure, Monitoring its Effects in Cardiac Surgery.

Hemodilution is a common perioperative practice. The deleterious effects of excessive hemodilution and subsequent edema formation have been well documented by numerous authors. Colloid oncotic pressure (COP) is a reliable clinical indicator of hemodilution in cardiac surgery. The intent of this study is to determine if a correlation exists between COP and various patient outcome variables. It would also be helpful to know if there is a particular COP value to avoid preventing or limiting patient morbidity. Blood samples from 61 adult patients (mean age = 70 years old) undergoing cardiopulmonary bypass surgery were collected for COP calculation and comparison. Sample collection was performed before heparinization, during cardiopulmonary bypass, at the conclusion of cardiopulmonary bypass, and in the intensive care unit. The resultant values obtained were used to generate a calculated COP. The lowest sustained COP was then compared with various patient outcome variables such as fluid balance, post-operative weight gain, post-operative blood loss, extubation time, length of stay, and blood products administered. A statistically significant difference (p < .05) was found between the COP and each of the monitored continuous variables. The data also suggest that maintaining a patient's COP at or above 15 mmHg could be desirable. Frequent monitoring of a patient's COP can provide a potential benefit to clinical decision making.

Therapeutic Drug Monitoring of Everolimus: A Consensus Report.

In 2014, the Immunosuppressive Drugs Scientific Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology called a meeting of international experts to provide recommendations to guide therapeutic drug monitoring (TDM) of everolimus (EVR) and its optimal use in clinical practice. EVR is a potent inhibitor of the mammalian target of rapamycin, approved for the prevention of organ transplant rejection and for the treatment of various types of cancer and tuberous sclerosis complex. EVR fulfills the prerequisites for TDM, having a narrow therapeutic range, high interindividual pharmacokinetic variability, and established drug exposure-response relationships. EVR trough concentrations (C0) demonstrate a good relationship with overall exposure, providing a simple and reliable index for TDM. Whole-blood samples should be used for measurement of EVR C0, and sampling times should be standardized to occur within 1 hour before the next dose, which should be taken at the same time everyday and preferably without food. In transplantation settings, EVR should be generally targeted to a C0 of 3-8 ng/mL when used in combination with other immunosuppressive drugs (calcineurin inhibitors and glucocorticoids); in calcineurin inhibitor-free regimens, the EVR target C0 range should be 6-10 ng/mL. Further studies are required to determine the clinical utility of TDM in nontransplantation settings. The choice of analytical method and differences between methods should be carefully considered when determining EVR concentrations, and when comparing and interpreting clinical trial outcomes. At present, a fully validated liquid chromatography tandem mass spectrometry assay is the preferred method for determination of EVR C0, with a lower limit of quantification close to 1 ng/mL. Use of certified commercially available whole-blood calibrators to avoid calibration bias and participation in external proficiency-testing programs to allow continuous cross-validation and proof of analytical quality are highly recommended. Development of alternative assays to facilitate on-site measurement of EVR C0 is encouraged.

Long-term evaluation of analytical methods used in sirolimus therapeutic drug monitoring.

Results of therapeutic monitoring of sirolimus blood concentrations are assay and laboratory dependent. This study compared performance over time of the IMx microparticle enzyme immunoassay (MEIA), Architect chemiluminescent microparticle immunoassay (CMIA), and liquid chromatography with mass spectrometric detection (LC/MS/MS) as part of a proficiency testing scheme. Pooled samples from sirolimus-treated patients and whole-blood samples spiked with known quantities of sirolimus were assayed monthly between 2004 and 2012. When results of pooled patient samples were compared with LC/MS/MS, the MEIA assay showed an overall mean percent bias of -2.3% ± 11.2% that, although initially positive, became increasingly negative from 2007 through 2009. The CMIA, which replaced the MEIA assay, had a mean percent bias of 21.9% ± 12.3%, remaining stable from 2007 through 2012. Similarly, for spiked samples, the MEIA showed an increasingly negative bias over time vs. LC/MS/MS, whereas CMIA maintained a stable positive bias. Based on comparison of immunoassay measurements on individual patient samples, CMIA values were more than 25% higher than MEIA values. These results highlight the importance of continued proficiency testing and regular monitoring of sirolimus assay performance. Clinicians must be aware of the methodology used and adjust target levels accordingly to avoid potential effects on efficacy and toxicity.

Has the new USP assay for heparin affected dosage for patients undergoing cardiopulmonary bypass?

In October 2009, the U.S. Pharmacopoeia (USP) changed the monograph for heparin to bring USP units in line with international units for heparin. The result was a 10% decrease in potency as measured by in vitro laboratory tests. This decrease led to questions regarding dosing guidelines. There existed a need for an in vivo study to determine the practical changes that may need to be implemented in regard to heparin administration for cardiopulmonary bypass in the clinical setting. A retrospective study was conducted to determine the heparin dose administered and the corresponding effect on patients undergoing coronary artery bypass grafting surgery using cardiopulmonary bypass. The study compared the heparin dose requirements and activated clotting time (ACT) results using the heparin before and after the USP changes. An analysis of the data was performed to determine the increased heparin dose required to achieve the same effect as before the USP change. This new heparin dosing protocol was instituted at Concord Hospital, Concord, NH. A prospective study was then preformed to verify the effects of the dosing change. In the new heparin group, the postheparin ACT fell by 9.1% (p = .028) and the patients achieving an ACT > 479 seconds fell by 12.8% as compared with the old heparin group. After adjustment of the loading dose calculation for heparin, the prospective study demonstrated the postheparin ACT (p = .684) and the percentage of patients achieving an ACT > 479 seconds (p = 1.000) to be similar to the values obtained before the USP change. An increase of the loading dose of approximately 12% is needed to achieve the patient effects seen before the UPS change.

Simultaneous determination of tramadol, O-desmethyltramadol and N-desmethyltramadol in human urine by gas chromatography-mass spectrometry.

Analytical procedures for the determination of tramadol (T), O-desmethyltramadol (ODT), and N-desmethyltramadol (NDT) in human urine have been developed and validated using gas chromatography-mass spectrometry (GC/MS). Sample preparation involved liquid-liquid extraction with methyl-tert-butyl ether (MTBE) and followed by back extraction with 0.1 M hydrochloric acid. Proadifen (SKF525A) was selected as internal standard (IS). Extraction efficiencies of T, ODT and NDT were 102.12, 101.30, and 98.21%, respectively. The calibration curves were linear (r(2)>0.99) in the concentration range 10-1000 ng/mL for all compounds. Limits of quantification (LOQ) were 10, 10 and 20 ng/mL for T, ODT and NDT, respectively. Intra-assay precision was within 1.29-6.48% and inter-assay precision was within 1.28-6.84% for T, ODT and NDT. Intra-assay accuracy was within 91.79-106.89% for all analytes. This method detected urine concentrations of T, ODT and NDT in six healthy volunteers for 7 days after administration of 50 mg oral doses of tramadol.

Randomized trial of the Terumo Capiox FX05 oxygenator with integral arterial filter versus Terumo Capiox Baby RX05 and Terumo Capiox AF02 arterial filter in infants undergoing cardiopulmonary bypass.

UNLABELLED: The purpose of this clinical trial was to evaluate the effect of the Terumo Capiox FX05 oxygenator with integrated arterial filter during cardiopulmonary bypass (CPB) compared with the Terumo Capiox RX05 Baby RX and arterial filter on inflammatory mediators and blood product utilization. Forty patients weighing less than 10 kg who underwent congenital heart surgery utilizing cardiopulmonary bypass were randomized into either oxygenator group. The endpoints included measuring inflammatory markers at six different time points (preoperative baseline, CPB circuit being primed, 15 minutes after CPB initiation, status post protamine administration, prior to transport to intensive care unit, and within 12 to 24 hours post surgery), blood product utilization, extubation time, and days until discharge. The inflammatory mediators showed no significant differences between oxygenators at any time points. However, looking at the inflammatory mediators of both the FX and RX groups combined, a statistically significant difference was seen in interleukin (IL)-6 at 12/24 hour post surgery (p < .001) versus baseline and all other time points. IL-8 at status post protamine (p < .001) and 12/24 hours post surgery (p < .001) demonstrated significant differences versus all other time points, and IL-10 at status post protamine (p < .001) and prior to leaving the operating room (p < .001) were statistically different compared to all other time points. Cardiopulmonary bypass stimulates the systemic inflammatory response through various components of the extracorporeal system. This investigation did not find significant differences in cytokines interferon-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, tumor necrosis factor (TNF)-alpha, and TNF-beta when comparing these two oxygenators. It is well known that various mechanisms contribute to the levels of cytokines circulating in a patient's blood volume and many manipulations throughout cardiac surgery have the ability to demonstrate anti-inflammatory interventions. Further investigation is needed as to how modification of the extracorporeal circuit may minimize increases in inflammatory mediators. KEYWORDS: infant, bypass, cytokines, blood, infant perfusion strategy.

Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine.

Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a 'cytokine storm', leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS. Previously healthy piglets (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (PCR/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells. TNF-alpha and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately after the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may have an important pathophysiological role in ECMO-related SIRS.

Delayed onset of seizures and toxicity associated with recreational use of Bromo-dragonFLY.

INTRODUCTION: Many countries have specific legislation, such as the Controlled Substances Act (1970) in the United States and the Misuse of Drugs Act (1971) in the United Kingdom to control recreational drugs. There is a growing market and supply of "novel" recreational drugs, which include the misuse of pharmaceutical compounds and research chemicals. These are often not covered under current legislation, despite the fact that they often have both similar chemical structures and/or clinical effects to controlled recreational drugs. CASE REPORT: A male patient presented to an emergency department with delayed onset of severe agitation, hallucinations, and tonic-clonic seizures following the use of Bromo-dragonFLY and an unknown white powder. He settled following IV benzodiazepines and supportive care, and was discharged with no evidence of long-term sequelae. Analysis of the white powder by gas chromatography/mass spectrometry (GC/MS), ultraviolet/visible spectrophotometry (UV/VIS) and thin layer chromatography (TLC) showed the presence of Bromo-dragonFLY (1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane); serum analysis by GC/MS and liquid chromatography with tandem mass spectrometry (LC/MS/MS) confirmed that a combination of Bromo-dragonFLY (0.95 ng/mL), ketamine (20 ng/mL) and cannabis had been used by the patient. No other recreational drugs were detected in an extensive toxicological screen of serum and urine samples. DISCUSSION: This is the first confirmed case to be reported of toxicity with delayed onset of severe agitation, hallucinations and tonic-clonic seizures associated with recreational use of Bromo-dragonFLY (1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane) in combination with ketamine and cannabis. In our view, this case provides further support for the need for a systematic approach to toxicological screening of patients with recreational drug toxicity, to identify emerging drugs and provide evidence for legislative authorities to assist in revising the legal status of emerging recreational drugs.

Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial.

BACKGROUND: Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. METHODS: Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite of biopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. RESULTS: Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). CONCLUSIONS: There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.

Methylene blue-induced methemoglobinemia during cardiopulmonary bypass? A case report and literature review.

The guanylate cyclase (GC) and inducible nitric oxide (iNOS) inhibitor methylene blue (MB) has been used in cardiac surgery patients for the treatment of a variety of conditions. Methylene blue has been successfully used for the prevention and treatment of vasoplegia syndrome (VS) in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Vasoplegia syndrome occurs in up to 10% of cardiac surgery patients and is associated with poor clinical outcomes. Vasoplegia syndrome is described along with the results of studies that have shown benefits of MB in the treatment of VS. These studies include the use of MB prior to CPB, when added to the CPB prime and when given into the CPB circuit during the operation. We report a case of emergency CPB on a 55-year-old male with bacterial endocarditis, scheduled for an AVR/MVR who arrested on arrival to the operating room. Once on CPB the patient developed a profound hypotension despite normal to high pump flows, with low systemic vascular resistance (SVR), which was refractory to vasopressors--consistent with a diagnosis of VS. Unbeknownst to the perfusionist, the patient was treated with MB which was immediately followed by an apparent sudden arterial desaturation, despite oxygenator ventilation with 100% oxygen (O2), and development of severe metabolic acidosis. Troubleshooting the cause of the apparent desaturation and eventual diagnosis of a false indication of arterial oxygen desaturation and methemoglobinemia (MHgb) due to MB injection is described. Methemoglobinemia is explained as well as its presentation and treatment with MB. The importance of intraoperating room communication and knowledge of drug effects are discussed.

Does zero balance ultrafiltration decrease the incidence of post-cardiopulmonary bypass atrial fibrillation?

Atrial fibrillation is the most frequent cardiac dysrhythmia after cardiac surgery. Postoperative atrial fibrillation (Afib) is shown to increase risk of stroke, congestive heart failure, and hemodynamic instability leading to increased hospital length of stay and cost. Inflammation and degenerative histologic changes in cell structure because of age may predispose patients to a higher susceptibility. Cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome (SIRS) responsible for a number of postoperative complications including arrhythmias. Zero balance ultrafiltration (ZBUF) has been shown to decrease SIRS by removing some of its mediators and products from the blood. The purpose of this retrospective analysis is to determine whether ZBUF does decrease the incidence of Afib after CPB. Retrospective review was conducted on consecutive primary coronary artery bypass patients placed on CPB from the period of January 2004 to June 2006. Data were collected from perfusion records, patient charts, blood bank records, and a cardiac surgery clinical database consisting of patient demographics, occurrence of postoperative Afib, ZBUF, blood product administration, antifibrinolytic use, bypass and aortic cross-clamp times, comorbidities, personnel, postoperative time on ventilator, and postoperative length of stay. Univariate analysis was performed on all numerical and categorical data for possible inclusion into a regression model for a p value of .05. New onset postoperative Afib was found in 48 patients (27%). One hundred twenty-seven patients (73%) did not develop postoperative Afib. The variables age and gender remained with odds ratio point estimates indicating that for every unit increase in age, the odds of Afib increased by a factor of 1.078. The odds of Afib increase by 2.629 for female gender. Statistical analysis did not prove the hypothesis, but did show that older age and female gender play a role in the occurrence of postoperative Afib.

Influence of intraoperative fluid volume on cardiopulmonary bypass hematocrit and blood transfusions in coronary artery bypass surgery.

A hematocrit (Hct) of less than 25% during cardiopulmonary bypass (CPB) and transfusion of homologous packed red blood cells (PRBC) are each associated with an increased probability of adverse events in cardiac surgery. Although the CPB circuit is a major contributor to hemodilution intravenous (IV) fluid volume may also significantly influence the level of hemodilution. The objective of this study was to explore the influence of asanguinous IV fluid volume on CPB Hct and intraoperative PRBC transfusion. After Institutional Review Board approval, a retrospective chart review of 90 adult patients that had undergone an elective, isolated CABG with CPB was conducted. Regression analysis was used to determine if pre-CPB fluid volume was associated with the lowest CPB Hct and the incidence of an intraoperative PRBC transfusion. In separate multivariate analyses, higher pre-CPB fluid volume was associated with lower minimum CPB Hct (p < .0001), and higher minimum CPB Hct was associated with a decreased probability of PRBC transfusion (p < .0001). Compared to patients that received <1600 mL (n = 55) of pre-CPB fluid, those that received >1600 mL (n = 35) had a decreased mean low CPB Hct (22.4% vs 25.6%, p < .0001), an increased incidence of a CPB Hct <25% (74% vs. 38%, p = .0008) and PRBC transfusion (60% vs. 16%, p < .0001), and increased median PRBC units transfused (2.0 vs 1.0, p = .1446) despite no significant difference in gender, age, patient size, baseline Hct, or CPB prime volume. Patients that received a PRBC transfusion (n = 30) received a significantly higher volume of pre-CPB fluid than nontransfused patients (1800 vs. 1350 mL, p = .0039). These findings suggest that pre-CPB fluid volume can significantly contribute to hemodilutional anemia in cardiac surgery. Optimizing pre-CPB volume may preserve baseline Hct and help limit intraoperative hemodilution.

Pharmacogenetics of immunosuppressive drugs: prospect of individual therapy for transplant patients.

The immunosuppressive drugs used in solid-organ transplantation are potent and toxic agents with narrow therapeutic ranges. Underdosing is associated with immunological rejection of the transplanted organ, whereas overdosing results in infections, malignancy and direct toxicity to a number of organs. Pharmacokinetic heterogeneity makes initial dose determination difficult, as there is a poor correlation between dose and blood concentration. Therapeutic drug monitoring is available but the pharmacokinetic-pharmacodynamic association is imperfect and it does not help in achieving target blood concentrations during the critical early 2-3 days after transplantation. Genetic polymorphisms in drug targets, drug-metabolizing enzymes and drug efflux pumps have been identified as potential targets for developing a pharmacogenetic strategy to individualize initial drug choice and dose. To date, use of the CYP3A5 genotype to predict the appropriate initial dose of tacrolimus is the most promising option for individualization of drug therapy in organ transplantation.

Effects of modified ultrafiltration on coagulation as measured by the thromboelastograph.

Hemodilution during cardiopulmonary bypass (CPB) continues to be a cause of morbidity associated with coagulation dysfunction, bleeding, and allogeneic blood transfusion. Clot formation and strength have been shown to impact bleeding and transfusions. Strategies to reduce hemodilution may be negated based on the course of the cardiac procedure itself. Modified ultrafiltration (MUF) is commonly used in pediatric cardiac surgery; however, it is not well accepted in adult surgery. This study aimed to evaluate clot formation and strength, bleeding, and transfusions in adult subjects undergoing MUF. Nineteen subjects having primary coronary artery bypass, aortic, or mitral valve surgeries were recruited and randomized to having MUF (n = 10) or no-MUF (n = 9) performed after the termination of CPB. Five time points for data collection were designated: T1, baseline/induction; T2, termination CPB; T3, post-MUF; T4, post-protamine; T5, 24 hours postoperative. Subjects randomized to MUF had 1505 +/- 15.8 mL of effluent removed, and no-MUF subjects had the CPB remnants processed with a cell salvage device. There was no statistical difference seen in 24-hour chest tube output, thromboelastograph values, or allogeneic transfusions at any time point between MUF and no-MUF subjects. There was a significant difference between MUF and no-MUF in the number of autologous cell salvage units processed (1.3 +/- .48 vs. 2.9 +/- .78, p = .0013) and end of procedure net fluid balance (+2003 +/- 1211 vs. +4194 +/- 1276 mL, p = .001), respectively. Estimated plasma loss from the cell salvage device was 477.6 mL greater in the no-MUF group. In primary adult cardiac procedures, MUF did not change coagulation values as measured by thromboelastography, number of allogeneic unit transfusions, or chest tube output at 24 hours postoperatively. There was a significant difference in autologous cell salvage units processed and end of procedure net fluid balance that benefited MUF subjects.

Use of recombinant factor VIIa (NovoSeven) in pediatric cardiac surgery.

Significant post-operative bleeding can be encountered in a small population of pediatric surgical patients requiring cardiopulmonary bypass (CPB). Recombinant factor VIIa (NovoSeven) has been advocated as a possible off-label rescue therapy for these individuals when conventional blood component therapy alone is inadequate. This study retrospectively evaluates rFVIIa administration for the treatment of severe bleeding in pediatric patients immediately after cardiac surgical procedures requiring CPB. The records of 15 patients receiving rFVIIa for excessive rates of bleeding refractory to conventional blood component therapy were studied. Blood product utilization, rates of blood loss, and evidence of pathologic sequelae were compared with matched historical controls in retrospective fashion. NovoSeven doses ranged from 76 to 282 microg/kg (group 1 < 30 kg) and 26 to 956 microg/kg (group 2 > 30 kg). Blood product administration patterns were not significantly different (p > .05) in the intensive care unit (ICU) between patient groups receiving rFVIIa and those not treated. Bleeding rates (mL/kg/h) for the first 2 hours after admission to the ICU remained statistically unchanged but were significantly increased for those time periods > 3 hours in patients < 30 kg treated with NovoSeven. Patients > 30 kg did not exhibit statistical differences in the rate of bleeding or the administration of blood products compared with matched controls. A significant reduction in prothrombin time (p = .001) and partial thromboplastin time (p = .02) was noted in patients < 30 kg receiving rFVIIa. There were no pathologic sequelae directly attributed to the administration of rFVIIa in any patients treated. Trends in the improvement of bleeding disturbances were noted in the ICU in patients < 30 kg treated with rFVIIa, subsequent to blood component therapy. The rate of bleeding (mL/kg/h) was improved in patients < 30 kg for the first 2 hours in the ICU. For individuals > 30 kg, there was no apparent benefit from the administration of rFVIIa.

Are there benefits to a fresh whole blood vs. packed red blood cell cardiopulmonary bypass prime on outcomes in neonatal and pediatric cardiac surgery?

Techniques for pediatric cardiac surgery requiring cardiopulmonary bypass (CPB) have significantly improved over the years. The use of fresh whole blood (FWB) and pre-bypass ultrafiltration (PBUF) has been suggested as means for improving perioperative and postoperative outcomes. It is the intent of this study to show that fresh whole blood along with PBUF will result in balanced CPB prime that can offer a reduction in blood product exposures and blood loss along with improving several measured postoperative outcomes. After institutional review board approval, a retrospective review was conducted on 100 patients to analyze the benefits of FWB and PBUF on outcomes in neonatal and pediatric cardiac surgery. Data analysis included preoperative and CPB data, perioperative inotrope and blood product exposure, and postoperative blood loss and blood product exposure measured for up to a 12-hour period in the intensive care unit (ICU). The three groups compared were FWB prime vs. packed red blood cell (PRBC) prime, < 5 kg FWB prime vs. < 5 kg PRBC prime, and 5+ kg FWB prime and 5+ kg PRBC prime. Cumulative blood product exposures for the FWB prime group found 62% received one blood exposure for the operative and postoperative period (p < .0001). The majority of patients who received a PRBC prime (64%) received three or more cumulative exposures (p < .0003). The < 5 kg FWB group also received significantly less cumulative blood exposure, with 64% receiving just one exposure. Comparatively, 85% of the < 5 kg PRBC patients received three or more blood product exposures perioperatively and postoperatively (p < .0001). Perioperative inotrope and postoperative blood loss did not differ among the groups. Outcomes for intraoperative death, intraoperative extubation, delayed sternal closure, and mediastinal reexploration were also not statistically different. The results of this study found that FWB leads to significantly less blood exposure, specifically in the < 5-kg population. Finally, the use of PBUF is an effective method for achieving a balanced, physiologic prime. Future research would be helpful in determining which specific patient populations would receive the greatest benefit from FWB and PBUF.

Pharmacogenetics as a tool for optimising drug therapy in solid-organ transplantation.

Existing immunosuppressive therapies used for solid-organ transplantation have narrow therapeutic indices, whereby underdosing is associated with acute immunological rejection of the transplanted organ and overdosing is associated with infections and malignancy, as well as organ-specific toxicities. There is significant inter-individual variation in the pharmacokinetics and pharmacodynamics of these drugs, an issue that has been addressed, in part, by therapeutic drug monitoring. Genetic polymorphisms in drug metabolising enzymes, drug efflux pumps and drug targets which may underly this heterogeneity have been identified and may provide a tool to guide prescribing. There are a number of associations between genotype and pharmacology, but as of now, only thiopurine-S-methyltransferase and cytochrome P450 3A5 have a sufficiently large influence to have potential in guiding therapy. Recent studies have also identified that donor genotype may play a significant role in immunosuppressive drug pharmacokinetics and pharmacodynamics.

Intraoperative assessment and quantification of coronary artery graft patency performed on or off cardiopulmonary bypass.

Within the last 10 years, the incorporation of off-pump coronary artery bypass grafting (OPCAB) into many surgical practices has grown. OPCAB requires the surgeon to operate on a beating heart, and it is generally accepted that OPCAB procedures are more technically demanding. Concerns of possible incomplete revascularizations and decreased graft patency have been noted in the literature. The objective of this study was to evaluate and compare on-pump and off-pump intraoperative coronary artery bypass graft (CABG) flow parameters. Intraoperative flow studies conducted with the Butterfly (Medi-Stim Norge AS, Oslo, Norway) flow meter were analyzed retrospectively on 74 patients. Comparisons were completed between patient groups having had their revascularizations performed on or off cardiopulmonary bypass. Our study revealed significant differences in the mean flow rate through saphenous vein grafts (SVG) to the obtuse marginal artery (OM; p = .014), to the diagonal artery (Diag; p = .003), to the right coronary artery (RCA; p = .001), and to the posterior descending artery (PDA; p = .001). Total blood product use showed significantly increased use of both platelets (PLTs) and cryoprecipitate (Cryo) in the on-pump group (p = .027 and .012, respectively). No differences were found for transfusions of red blood cells (RBCs) or fresh frozen plasma (FFP). Additional findings showed a significantly decreased median length of stay (LOS) for the off-pump group. The on-pump patients had a median hospital stay of 7 days (range, 4-24 days), whereas the off-pump patients had a median stay of 6 days (range, 3-22 days; p = .049). Although we were able to show some significance in the mean flow data supporting increased graft flow with the on-pump technique, we were not able to show an overall increase in all recorded flow characteristics to support one method over another.

Quality assessment of platelet rich plasma during anti-platelet therapy.

Platelet rich plasma (PRP) is being used with increased frequency in many surgical procedures for its known benefits of accelerated surgical wound site healing. Speculations in its efficacy in the presence of anti-platelet therapy have been proposed. To aid in defining a quality platelet rich plasma product in the presence of acetylsalicylic acid (ASA) and Plavix (clopidogrel bisulfate), we investigated three (3) groups (n = 18) of cardiac surgical patients receiving PRP. Platelet function test, platelet concentration, and quantification of growth factors (PDGF-bb and TGF-b1) were evaluated. Results showed no statistical evidence of decreased growth factors delivered to the surgical wound site in the presence of acetylsalicylic acid (ASA) and/or Plavix (clopidogrel bisulfate). Evidence in this pilot study supports the use of PRP for patients receiving Plavix and aspirin therapy without compromising the quantity of specific growth factors delivered to a wound site.

Hemoglobin test result variability and cost analysis of eight different analyzers during open heart surgery.

The purpose of this study was to compare the variation in hemoglobin (Hgb) values among various point-of-care (POC) analyzers available on the market. Eight analyzers (Gem 3000, ABL 720, ABL 77, Rapidpoint 405, IL 682, GemOPL, Hb 201+, and manual/centrifugation) were compared with the Hgb values from the Beckman Coulter LH750. A total of 72 patient samples were analyzed on each test instrument. The samples were obtained after intubation, after heparinization, during cardiopulmonary bypass, and after protamine administration. Four of the samples were excluded from the study because of delayed sample analysis. The calculated mean differences of reference test method Hgb (mean +/- SD) for all samples (n = 68) were Gem 3000 = 1.431 +/- 0.396 g/dL; ABL 720 = -0.224 +/- 0.240 g/dL; ABL 77 = 0.341 +/- 0.578 g/dL; Rapidpoint 405 = 0.001 +/- 0.205 g/dL; IL 682 = -0.137 +/- 0.232 g/dL; GemOPL = 0.774 +/- 0.427 g/dL; Hb 201+ = 0.110 +/- 0.524 g/dL; and manual/ centrifugation = 0.547 +/- 0.499 g/dL. Cumulative results indicated that the bias in Hgb values from the Gem 3000, ABL720, ABL 77, IL 682, GemOPL, and the manual method were statistically significant (p < .05), compared with the Coulter LH750. Additionally, only the Rapidpoint 405 and Hb 201+ most closely matched the values from the Coulter LH750 (p > .05). Some of the methodologies have previously been shown to be affected during hemodilution, hypoproteinemia, and/or after blood transfusion. There is variability among methodologies, which can give rise to statistically different Hgb values, and one should consider the "ideal" instrument based on this and many other factors. Based on our results, the rank order of closest approximation to the Coulter LH750 measurement was Rapidpoint 405, Hb 201+, IL 682, ABL 720, ABL 77, manual/centrifugation, GemOPL, and Gem 3000.