Michael P. Eaton

A survey of the use of ultrasound during central venous catheterization.

BACKGROUND:Complications during central venous catheterization (CVC) are not rare and can be serious. The use of ultrasound (US) during CVC has been recommended to improve patient safety. We performed a survey to evaluate the frequency of, and factors influencing, US use. METHODS:We conducted an electronic survey of all members of the Society of Cardiovascular Anesthesiologists. Univariate and multivariate logistic regressions were used to assess the association between the frequency of US use and hospital and physician factors. All tests were two-sided, and a P value <0.05 was considered statistically significant. RESULTS:Of the 4235 members, 1494 responded (response rate = 35.3%). Two-thirds of the respondents never, or almost never, use US, whereas only 15% always, or almost always, use US. Thirty-three percent of the respondents never, or almost never, have US available, whereas 41% stated that US is always, or almost always, available. Availability of US equipment was strongly associated with US use for CVC (adj OR = 18.9; P value <0.001). The most common reason cited for not using US was “no apparent need for the use of US” (46%). When US was used, rescue or screening approaches were more common (72%) than real-time use (26%). CONCLUSIONS:The use of US during CVC remains limited and is most strongly associated with the availability of equipment. Screening and rescue use of US are more common than real-time guidance. Our survey suggests that current use of US during CVC differs from existing evidence-based recommendations.

Antifibrinolytic Therapy in Surgery for Congenital Heart Disease

The efficacy of the serine protease inhibitor, aprotinin, and the lysine analogs, &egr;-aminocaproic acid and tranexamic acid, in reducing bleeding and transfusion in adults undergoing cardiac surgery is well established. Although children undergoing cardiac surgery are clearly at high risk for bleeding and transfusion, the risks and benefits of this therapy for the pediatric population are less well understood. There is a reasonable body of literature examining antifibrinolytic therapy in congenital heart surgery, but the large variability in patients studied, procedures, methods, and dosing schemes makes a quantitative analysis of this literature impractical. A qualitative review of this literature reveals significant support for the efficacy of all three drugs for decreasing bleeding and transfusion in congenital heart surgery, likely with more benefit in certain populations. Limited data suggest that there is no difference in efficacy among the three drugs, although aprotinin may have unique antiinflammatory effects that are of benefit in pediatric patients. There is not enough evidence to draw any conclusions about the safety of these drugs in children, although it appears that the risk of anaphylaxis with aprotinin in children may be less than in adults. Dosing schemes used for these drugs have been variable and not always based on sound pharmacologic principles, despite available pharmacokinetic and pharmacodynamic data. Further research should be directed toward establishing safety, evaluating the relative efficacy of the two classes of drugs, proving benefit in specific patient groups, and better defining effective dosing schemes.

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.

Objectives: Children undergoing cardiac surgery with cardiopulmonary bypass are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells and platelets transfused to these patients will reduce postoperative transfusion-related immune modulation and inflammation. Design: Prospective, randomized, controlled clinical trial. Setting: University hospital pediatric cardiac intensive care unit. Patients: Children from birth to 17 yrs undergoing cardiac surgery with cardiopulmonary bypass. Interventions: Children were randomized to an unwashed or washed red blood cells and platelet transfusion protocol for their surgery and postoperative care. All blood was leuko-reduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis preoperatively, immediately, and 6 and 12 hrs after cardiopulmonary bypass. Primary outcome was the 12-hr postcardiopulmonary bypass interleukin-6-to-interleukin-10 ratio. Secondary measures were interleukin levels, C-reactive protein, and clinical outcomes. Measurements and Main Results: One hundred sixty-two subjects were studied, 81 per group. Thirty-four subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hr interleukin ratio was significantly lower in the washed group (3.8 vs. 4.8; p = .04) secondary to lower interleukin-6 levels (after cardiopulmonary bypass: 65 vs.100 pg/mL, p = .06; 6 hrs: 89 vs.152 pg/mL, p = .02; 12 hrs: 84 vs.122 pg/mL, p = .09). Postoperative C-reactive protein was lower in subjects receiving washed blood (38 vs. 43 mg/L; p = .03). There was a numerical, but not statistically significant, decrease in total blood product transfusions (203 vs. 260) and mortality (2 vs. 6 deaths) in the washed group compared to the unwashed group. Conclusions: Washed blood transfusions in cardiac surgery reduced inflammatory biomarkers, number of transfusions, donor exposures, and were associated with a nonsignificant trend toward reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.

meperidine and Lidocaine Block of Recombinant Voltage-dependent Na+ Channels : Evidence that Meperidine is a Local Anesthetic

BACKGROUND The opioid meperidine induces spinal anesthesia and blocks nerve action potentials, suggesting it is a local anesthetic. However, whether it produces effective clinical local anesthesia in peripheral nerves remains unclear. Classification as a local anesthetic requires clinical local anesthesia but also blockade of voltage-dependent Na+ channels with characteristic features (tonic and phasic blockade and a negative shift in the voltage-dependence of steady-state inactivation) involving an intrapore receptor. The authors tested for these molecular pharmacologic features to explore whether meperidine is a local anesthetic. METHODS The authors studied rat skeletal muscle mu1 (RSkM1) voltage-dependent Na+ channels or a mutant form heterologously coexpressed with rat brain Na+ channel accessory beta1, subunit in Xenopus oocytes. Polymerase chain reaction was used for mutagenesis, and mutations were confirmed by sequencing. Na+ currents were measured using a two-microelectrode voltage clamp. Meperidine and the commonly used local anesthetic lidocaine were applied to oocytes in saline solution at room temperature. RESULTS Meperidine and lidocaine produced tonic current inhibition with comparable concentration dependence. Meperidine caused phasic current inhibition in which the concentration-response relationship was shifted to fivefold greater concentration relative to lidocaine. Meperidine and lidocaine negatively shifted the voltage dependence of steady-state inactivation. Mutation of a putative local anesthetic receptor reduced phasic inhibition by meperidine and lidocaine and tonic inhibition by lidocaine, but not meperidine tonic inhibition. CONCLUSIONS Meperidine blocks Na+ channels with molecular pharmacologic features of a local anesthetic. The findings support classification of meperidine as a local anesthetic but with less overall potency than lidocaine.

The impact of anesthesiologists on coronary artery bypass graft surgery outcomes.

BACKGROUND One of every 150 hospitalized patients experiences a lethal adverse event; nearly half of these events involves surgical patients. Although variations in surgeon performance and quality have been reported in the literature, less is known about the influence of anesthesiologists on outcomes after major surgery. Our goal of this study was to determine whether there is significant variation in outcomes between anesthesiologists after controlling for patient case mix and hospital quality. METHODS Using clinical data from the New York State Cardiac Surgery Reporting System, we conducted a retrospective observational study of 7920 patients undergoing isolated coronary artery bypass graft surgery. Multivariable logistic regression modeling was used to examine the variation in death or major complications (Q-wave myocardial infarction, renal failure, stroke) across anesthesiologists, controlling for patient demographics, severity of disease, comorbidities, and hospital quality. RESULTS Anesthesiologist performance was quantified using fixed-effects modeling. The variability across anesthesiologists was highly significant (P < 0.001). Patients managed by low-performance anesthesiologists (corresponding to the 25th percentile of the distribution of anesthesiologist risk-adjusted outcomes) experienced nearly twice the rate of death or serious complications (adjusted rate 3.33%; 95% confidence interval [CI], 3.09%-3.58%) as patients managed by high-performance anesthesiologists (corresponding to the 75th percentile) (adjusted rate 1.82%; 95% CI, 1.58%-2.10%). This performance gap was observed across all patient risk groups. CONCLUSIONS The rate of death or major complications among patients undergoing coronary artery bypass graft surgery varies markedly across anesthesiologists. These findings suggest that there may be opportunities to improve perioperative management to improve outcomes among high-risk surgical patients.

Children with single-ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy.

Objective: To examine the impact of a restrictive vs. liberal transfusion strategy on arterial lactate and oxygen content differences in children with single-ventricle physiology post cavopulmonary connection. Children with single-ventricle physiology are routinely transfused postoperatively to increase systemic oxygen delivery, and transfusion thresholds in this population have not been studied. Design: Prospective, randomized, controlled, clinical trial. Setting: Pediatric cardiac intensive care unit in a teaching hospital. Patients: Infants and children (n = 60) with variations of single-ventricle physiology presenting for cavopulmonary connection. Interventions: Subjects were randomized to a restrictive (hemoglobin of <9.0 g/dL), or liberal (hemoglobin of ≥13.0 g/dL) transfusion strategy for 48 hrs post operation. Primary outcome measures were mean and peak arterial lactate. Secondary end points were arteriovenous (C(a-v)o2) and arteriocerebral oxygen content (C(a-c)o2) differences and clinical outcomes. Measurements and Main Results: A total of 30 children were in each group. There were no significant preoperative differences. Mean hemoglobin in the restrictive and liberal groups were 11 ± 1.3 g/dL and 13.9 ± 0.5 g/dL, respectively (p < .01). No differences in mean (1.4 ± 0.5 mmol/L [Restrictive] vs. 1.4 ± 0.4 mmol/L [Liberal]) or peak (3.1 ± 1.5 mmol/L [Restrictive] vs. 3.2 ± 1.3 mmol/L [Liberal]) lactate between groups were found. Mean number of red blood cell transfusions were 0.43 ± 0.6 and 2.1 ± 1.2 (p < .01), and donor exposure was 1.2 ± 0.7 and 2.4 ± 1.1 to (p < .01), for each group, respectively. No differences were found in C(a-v)o2, C(a-c)o2, or clinical outcome measures. Conclusion: Children with single-ventricle physiology do not benefit from a liberal transfusion strategy after cavopulmonary connection. A restrictive red blood cell transfusion strategy decreases the number of transfusions, donor exposures, and potential risks in these children. Larger studies with clinical outcome measures are needed to determine the transfusion threshold for children post cardiac repair or palliation for congenital heart disease.

Variation of blood transfusion in patients undergoing major noncardiac surgery.

Objective: To examine the hospital variability in use of red blood cells (RBCs), fresh-frozen plasma (FFP), and platelet transfusions in patients undergoing major noncardiac surgery. Background: Blood transfusion is commonly used in surgical procedures in the United States. Little is known about the hospital variability in perioperative transfusion rates for noncardiac surgery. Methods: We used the University HealthSystem Consortium database (2006–2010) to examine hospital variability in use of allogeneic RBC, FFP, and platelet transfusions in patients undergoing major noncardiac surgery. We used regression-based techniques to quantify the variability in hospital transfusion practices and to study the association between hospital characteristics and the likelihood of transfusion. Results: After adjusting for patient risk factors, hospital transfusion rates varied widely for patients undergoing total hip replacement (THR), colectomy, and pancreaticoduodenectomy. Compared with patients undergoing THR in average-transfusion hospitals, patients treated in high-transfusion hospitals have a greater than twofold higher odds of being transfused with RBCs [adjusted odds ratio (AOR) = 2.41; 95% confidence interval (CI), 1.89–3.09], FFP (AOR = 2.81; 95% CI, 2.02–3.91), and platelets (AOR = 2.52; 95% CI, 1.95–3.25), whereas patients in low-transfusion hospitals have an approximately 50% lower odds of receiving RBCs (AOR = 0.45; 95% CI, 0.35–0.57), FFP (AOR = 0.37; 95% CI, 0.27–0.51), and platelets (AOR = 0.42; 95% CI, 0.29–0.62). Similar results were obtained for colectomy and pancreaticoduodenectomy. Conclusions: There was dramatic hospital variability in perioperative transfusion rates among patients undergoing major noncardiac surgery at academic medical centers. In light of the potential complications of transfusion therapy, reducing this variability in hospital transfusion practices may result in improved surgical outcomes.

Coagulation considerations for infants and children undergoing cardiopulmonary bypass

Cardiac surgery involving cardiopulmonary bypass imposes a significant pathophysiologic burden on patients. Pediatric patients are especially predisposed to the adverse effects of surgery and bypass on the coagulation system, with resultant bleeding, transfusion, and poor outcomes. These risks accrue to pediatric patients in inverse proportion to their weight and are attributable to hematologic immaturity, coagulation defects associated with congenital heart disease, bypass equipment, and the nature of congenital heart surgery. Standard anticoagulation does not completely inhibit thrombin generation, and continuous consumption of coagulation factor continues throughout bypass. Conventional measurements of anticoagulation during bypass poorly reflect this incomplete anticoagulation, and alternate methods may improve anticoagulant therapy. Emerging therapies for blocking the effects of bypass on the coagulation system hold promise for decreasing bleeding and related complications, and improving outcomes in congenital heart surgery.

Preoperative thrombocytopenia and postoperative outcomes after noncardiac surgery.

Background:Most studies examining the prognostic value of preoperative coagulation testing are too small to examine the predictive value of routine preoperative coagulation testing in patients having noncardiac surgery. Methods:Using data from the American College of Surgeons National Surgical Quality Improvement database, the authors performed a retrospective observational study on 316,644 patients having noncardiac surgery who did not have clinical indications for preoperative coagulation testing. The authors used multivariable logistic regression analysis to explore the association between platelet count abnormalities and red cell transfusion, mortality, and major complications. Results:Thrombocytopenia or thrombocytosis occurred in 1 in 14 patients without clinical indications for preoperative platelet testing. Patients with mild thrombocytopenia (101,000–150,000 µl−1), moderate-to-severe thrombocytopenia (<100,000 µl−1), and thrombocytosis (≥450,000 µl−1) were significantly more likely to be transfused (7.3%, 11.8%, 8.9%, 3.1%) and had significantly higher 30-day mortality rates (1.5%, 2.6%, 0.9%, 0.5%) compared with patients with a normal platelet count. In the multivariable analyses, mild thrombocytopenia (adjusted odds ratio [AOR], 1.28; 95% CI, 1.18–1.39) and moderate-to-severe thrombocytopenia (AOR, 1.76; 95% CI, 1.49–2.08), and thrombocytosis (AOR, 1.44; 95% CI, 1.30–1.60) were associated with increased risk of blood transfusion. Mild thrombocytopenia (AOR, 1.31; 95% CI, 1.11–1.56) and moderate-to-severe thrombocytopenia (AOR, 1.93; 95% CI, 1.43–2.61) were also associated with increased risk of 30-day mortality, whereas thrombocytosis was not (AOR, 0.94; 95% CI, 0.72–1.22). Conclusion:Platelet count abnormalities found in the course of routine preoperative screening are associated with a higher risk of blood transfusion and death.

The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro.

BACKGROUND:Neonates are at high risk for bleeding complications after cardiovascular surgery. Activation of intravascular fibrinolysis is one of the principal effects of cardiopulmonary bypass that causes poor postoperative hemostasis. Antifibrinolytic medications such as tranexamic acid are often used as prophylaxis against fibrinolysis, but concentration/effect data to guide dosing are sparse for adults and have not been published for neonates. Higher concentrations of tranexamic acid than those necessary for inhibition of fibrinolysis may have adverse effects. Therefore, we investigated the concentration of tranexamic acid necessary to inhibit activated fibrinolysis in neonatal plasma. METHODS:We conducted an in vitro study using neonatal plasma derived from the placenta/cord units from 20 term, elective cesarean deliveries. Graded concentrations of tranexamic acid were added to aliquots of the pooled plasma before maximally activating fibrinolysis with high-dose tissue-type plasminogen activator. Thromboelastography was then performed with the primary outcome variable being lysis at 30 minutes. These procedures were repeated on pooled adult normal plasma and dilutions of neonatal plasma. RESULTS:The minimum concentrations of tranexamic acid to completely prevent fibrinolysis were 6.54 &mgr;g/mL (95% confidence interval, 5.19–7.91) for neonatal plasma and 17.5 &mgr;g/mL (95% confidence interval, 14.59–20.41) for adult plasma. Neonatal plasma requires a significantly lower concentration than adult plasma (P < 0.0001, 2-sided Wald test). CONCLUSIONS:Our data establish the minimal effective concentration of tranexamic acid necessary to completely prevent fibrinolysis in neonatal plasma in vitro. These data may be useful in designing a dosing scheme for tranexamic acid appropriate for neonates.