Exploring Noncardiac Surgical Needs From Infancy to Adulthood in Patients With Congenital Heart Disease.

OBJECTIVES: As life expectancy for patients born with congenital heart disease (CHD) continues to rise, these patients will present increasingly for noncardiac surgery during childhood and adolescence. This study aimed to map the lifespan of noncardiac surgical needs among patients with CHD and explore how these needs may change over time. DESIGN: All patients with CHD presenting for noncardiac surgery between 2008 and 2014 were selected for review. SETTING: The study was conducted at a single urban academic tertiary pediatric hospital. PARTICIPANTS: All patients with CHD presenting for noncardiac surgery during the study period were included and grouped by cardiac diagnosis. INTERVENTIONS: Descriptive analysis included patient demographics, CHD diagnosis, procedures performed, and clinical data, including baseline saturation and underlying cardiac function. MEASUREMENTS AND MAIN RESULTS: A total of 3,011 noncardiac surgical procedures were performed on patients with CHD during the study period. The most common CHD diagnoses were patent ductus arteriosus (27.6%), ventricular septal defects (24.7%), and patent foramen ovale (24.3%). The median age was 4 years, 87% of all the patients were ≤10 years, and 41% had associated syndromes. Of the patients, 76% underwent a preoperative echocardiogram, and 10% had depressed cardiac function at the time of surgery. The most common procedures performed were ear, nose, and throat (20%), general surgery (14%), and radiology (11%). Intraoperative events were reported in 488 out of 3,010 encounters (16.2%), with the highest rates reported in patients with single-ventricle physiology (55/179; 30.7%). CONCLUSIONS: These findings suggested a greater burden of noncardiac surgery in lower age groups, with ear, nose, and throat and general surgery most common in young children and orthopedic and dental procedures increasing in adolescence.

The Characterization of Postoperative Mechanical Respiratory Requirement in Neonates and Infants Undergoing Cardiac Surgery on Cardiopulmonary Bypass in a Single Tertiary Institution.

OBJECTIVES: Although neonates and infants undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at high risk of developing perioperative morbidity and mortality, including lung injury, the intraoperative profile of lung injury in this cohort is not well-described. Given that the postoperative course of patients in the pediatric cardiac surgical arena has become increasingly expedited, the objective of this study was to characterize the profiles of postoperative mechanical ventilatory support in neonates and infants undergoing cardiac surgery on CPB and to examine the characteristics of lung mechanics and lung injury in this patient population who are potentially amendable to early postoperative recovery in a single tertiary pediatric institution. DESIGN: A retrospective data analysis of neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. SETTING: A single-center, university teaching hospital. PARTICIPANTS: The study included 328 neonates and infants who underwent cardiac surgery on cardiopulmonary bypass. INTERVENTIONS: A subset of 128 patients were studied: 58 patients undergoing ventricular septal defect (VSD) repair, 36 patients undergoing complete atrioventricular canal (CAVC) repair, and 34 patients undergoing bidirectional Glenn (BDG) shunt surgery. MEASUREMENTS AND MAIN RESULTS: Of the entire cohort, 3.7% experienced in-hospital mortality. Among all surgical procedures, VSD repair (17.7%) was the most common, followed by CAVC repair (11.0%) and BDG shunt surgery (10.4%). Of patients who underwent VSD repair, CAVC repair, and BDG shunt surgery, 65.5%, 41.7%, and 67.6% were off mechanical ventilatory support within 24 hours postoperatively, respectively. In all three of the surgical repairs, lung compliance decreased after CPB compared to pre-CPB phase. Sixty point three percent of patients with VSD repair and 77.8% of patients with CAVC repair showed a PaO2/FIO2 (P/F) ratio of <300 after CPB. Post- CPB P/F ratios of 120 for VSD patients and 100 for CAVC patients were considered as optimal cutoff values to highly predict prolonged (>24 hours) postoperative mechanical ventilatory support. A higher volume of transfused platelets also was associated with postoperative ventilatory support ≥24 hours in patients undergoing VSD repair, CAVC repair, and BDG shunt surgery. CONCLUSIONS: There was a high incidence of lung injury after CPB in neonates and infants, even in surgeries amendable for early recovery. Given that CPB-related factors (CPB duration, crossclamp time) and volume of transfused platelet were significantly associated with prolonged postoperative ventilatory support, the underlying cause of cardiac surgery-related lung injury can be multi-factorial.

Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung.

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin.

Volatile Anesthetic Sevoflurane Attenuates Toll-Like Receptor 1/2 Activation.

BACKGROUND: Although immunomodulatory effects of anesthetics have been increasingly recognized, their underlying molecular mechanisms are not completely understood. Toll-like receptors (TLRs) are one of the major receptors to recognize invading pathogens and danger signals from damaged host tissues to initiate immune responses. Among the TLR family, TLR2 and TLR4 recognize a wide range of ligands and are considered to be important players in perioperative pathophysiology. Based on our recent finding that volatile anesthetics modulate TLR4 function, we tested our hypothesis that they would also modulate TLR2 function. METHODS: The effect of anesthetics isoflurane, sevoflurane, propofol, and dexmedetomidine on TLR2 activation was examined by reporter assays. An anesthetic that affected the activation was subjected to in silico rigid docking simulation on TLR2. To test our prediction that sevoflurane and a TLR1/TLR2 ligand Pam3CSK4 would compete for the same pocket of TLR2, we performed Pam3CSK4 competitive binding assay to TLR2 using HEK cells stably transfected with TLR2 (HEK-TLR2) with or without sevoflurane. We examined the effect of different anesthetics on the functions of human neutrophils stimulated with TLR2 ligands. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis. RESULTS: We observed that the attenuation of TLR1/TLR2 activation was seen on sevoflurane exposure but not on isoflurane, propofol, or dexmedetomidine exposure. The attenuation of TLR2/TLR6 activation was not seen in any of the anesthetics tested. The rigid docking simulation predicted that sevoflurane and Pam3CSK4 bound to the same pocket of TLR1/TLR2 complex. The binding of Pam3CSK4 to HEK-TLR2 cells was impaired in the presence of sevoflurane, indicating that sevoflurane and Pam3CSK4 competed for the pocket, as predicted in silico. The stimulation of neutrophils with Pam3CSK4 induced L-selection shedding but did not affect phagocytosis and reactive oxygen species production. L-selectin shedding from neutrophils was attenuated only by sevoflurane, consistent with the result of our reporter assays. CONCLUSIONS: We found that TLR1/TLR2 activation was attenuated by sevoflurane, but we found no evidence for attenuation by isoflurane, propofol, or dexmedetomidine at clinically relevant concentrations. Our structural analysis and competition assay supported that sevoflurane directly bound to TLR2 at the interphase of the TLR1/TLR2 complex. Sevoflurane attenuated neutrophil L-selectin shedding, an important step for neutrophil migration.

The "Mother of pediatric cardiac anesthesia": An interview with Dr Dolly D. Hansen, a pioneering woman in medicine.

Dr Dolly D. Hansen (1935-), Associate Professor in the Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital and Harvard Medical School, devoted her life to improving the perioperative care of children with congenital heart disease. She applied her knowledge of cardiovascular and pulmonary physiology and the effects on anesthetic agents in children with and without heart disease into clinical practice and thereby greatly influenced the practice of pediatric anesthesia, cardiology, surgery, and critical care medicine. As an exceptional master clinician, leader, program builder, innovator, teacher, and academic role model, she shaped the careers of hundreds of fellows and young attendings, many of whom became leaders in the field.

Intraluminal Pulmonary Vein Stenosis in Children: A "New" Lesion.

Pulmonary vein stenosis (PVS) is a rare disorder that leads to progressive narrowing of the extrapulmonary veins. PVS has been reported in both children and adults and in its worse iteration leads to pulmonary hypertension, right ventricular failure, and death. Multiple etiologies of PVS have been described in children and adults. This review will focus on intraluminal PVS in children. Intraluminal PVS has an estimated incidence ranging from 0.0017% to 0.03%. It is associated with conditions such as prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, Smith-Lemli-Opitz syndrome, and Down syndrome. Cardiac catheterization and pulmonary vein angiography are the gold standard for diagnosis and anatomic delineation. Other imaging modalities including magnetic resonance imaging, chest tomography, and transesophageal echocardiography are increasingly being used. Mortality of PVS in children is approximately 50%. Predictors of mortality include involvement of ≥3 pulmonary veins, bilateral pulmonary vein involvement, onset of PVS in infancy, elevated pulmonary artery pressure or systolic pulmonary artery-to-aortic pressure ratio, right ventricular dysfunction, restenosis after surgery, distal/upstream disease, and disease progression to previously uninvolved pulmonary veins. Treatment includes catheter-based pulmonary vein dilations with or without stenting, surgical interventions, medical therapy, and in some instances, lung transplantation. Cardiac catheterization for PVS involves a comprehensive hemodynamic and anatomic assessment of the pulmonary veins as well as therapeutic transcatheter interventions. Several surgical strategies have been used. Sutureless repair is currently most commonly used, but patch venoplasty, endarterectomy, ostial resection, and reimplantation are used in select circumstances as well. Medical therapies such as imatinib mesylate and bevacizumab are increasingly being used in an effort to suppress the myofibroblastic proliferation seen in PVS patients. Lung transplantation has been used as an alternative treatment strategy for end-stage, refractory PVS. Nonetheless, despite the different innovative approaches used, morbidity and mortality remain high. At present, the preferred treatment strategy is frequent reassessment of disease progression to guide use of catheter-based and surgical interventions in conjunction with medical therapy.

Incidence and Risk Factors for Perioperative Cardiovascular and Respiratory Adverse Events in Pediatric Patients With Congenital Heart Disease Undergoing Noncardiac Procedures.

BACKGROUND: While mortality and adverse perioperative events after noncardiac surgery in children with a broad range of congenital cardiac lesions have been investigated using large multiinstitutional databases, to date single-center studies addressing adverse outcomes in children with congenital heart disease (CHD) undergoing noncardiac surgery have only included small numbers of patients with significant heart disease. The primary objective of this study was to determine the incidences of perioperative cardiovascular and respiratory events in a large cohort of patients from a single institution with a broad range of congenital cardiac lesions undergoing noncardiac procedures and to determine risk factors for these events. METHODS: We identified 3010 CHD patients presenting for noncardiac procedures in our institution over a 5-year period. We collected demographic information, including procedure performed, cardiac diagnosis, ventricular function as assessed by echocardiogram within 6 months of the procedure, and classification of CHD into 3 groups (minor, major, or severe CHD) based on residual lesion burden and cardiovascular functional status. Characteristics related to conduct of anesthesia care were also collected. The primary outcome variables for our analysis were the incidences of intraoperative cardiovascular and respiratory events. Univariable and multivariable logistic regressions were used to determine risk factors for these 2 outcomes. RESULTS: The incidence of cardiovascular events was 11.5% and of respiratory events was 4.7%. Univariate analysis and multivariable analysis demonstrated that American Society of Anesthesiologists (≥3), emergency cases, major and severe CHD, single-ventricle physiology, ventricular dysfunction, orthopedic surgery, general surgery, neurosurgery, and pulmonary procedures were associated with perioperative cardiovascular events. Respiratory events were associated with American Society of Anesthesiologists (≥4) and otolaryngology, gastrointestinal, general surgery, and maxillofacial procedures. CONCLUSIONS: Intraoperative cardiovascular events and respiratory events in patients with CHD were relatively common. While cardiovascular events were highly associated with cardiovascular status, respiratory events were not associated with cardiovascular status.

SCAI/CCAS/SPA expert consensus statement for anesthesia and sedation practice: Recommendations for patients undergoing diagnostic and therapeutic procedures in the pediatric and congenital cardiac catheterization laboratory.

Current practice of sedation and anesthesia for patients undergoing pediatric congenital cardiac catheterization laboratory (PCCCL) procedures is known to vary among institutions, a multi-society expert panel with representatives from the Congenital Heart Disease Council of the Society for Cardiovascular Angiography and Interventions (SCAI), the Society for Pediatric Anesthesia (SPA) and the Congenital Cardiac Anesthesia Society (CCAS) was convened to evaluate the types of sedation and personnel necessary for procedures performed in the PCCCL. The goal of this panel was to provide practitioners and institutions performing these procedures with guidance consistent with national standards and to provide clinicians and institutions with consensus-based recommendations and the supporting references to encourage their application in quality improvement programs. Recommendations can neither encompass all clinical circumstances nor replace the judgment of individual clinicians in the management of each patient. The science of medicine is rooted in evidence, and the art of medicine is based on the application of this evidence to the individual patient. This expert consensus statement has adhered to these principles for optimal management of patients requiring sedation and anesthesia. What follows are recommendations for patient monitoring in the PCCCL regardless of whether minimal or no sedation is being used or general anesthesia is being provided by an anesthesiologist. © 2016 Wiley Periodicals Inc.

Anesthesiologist- and System-Related Risk Factors for Risk-Adjusted Pediatric Anesthesia-Related Cardiac Arrest.

BACKGROUND: Pediatric anesthesia-related cardiac arrest (ARCA) is an uncommon but potentially preventable adverse event. Infants and children with more severe underlying disease are at highest risk. We aimed to identify system- and anesthesiologist-related risk factors for ARCA. METHODS: We analyzed a prospectively collected patient cohort data set of anesthetics administered from 2000 to 2011 to children at a large tertiary pediatric hospital. Pre-procedure systemic disease level was characterized by ASA physical status (ASA-PS). Two reviewers independently reviewed cardiac arrests and categorized their anesthesia relatedness. Factors associated with ARCA in the univariate analyses were identified for reevaluation after adjustment for patient age and ASA-PS. RESULTS: Cardiac arrest occurred in 142 of 276,209 anesthetics (incidence 5.1/10,000 anesthetics); 72 (2.6/10,000 anesthetics) were classified as anesthesia-related. In the univariate analyses, risk of ARCA was much higher in cardiac patients and for anesthesiologists with lower annual caseload and/or fewer annual days delivering anesthetics (all P < 0.001). Anesthesiologists with the highest academic rank and years of experience also had higher odds of ARCA (P = 0.02). After risk adjustment for ASA-PS ≥ III and age ≤ 6 months, however, the association with lower annual days delivering anesthetics remained (P = 0.03), but the other factors were no longer significant. CONCLUSIONS: Case-mix explained most associations between higher risk of pediatric ARCA and anesthesiologist-related variables at our institution, but the association with fewer annual days delivering anesthetics remained. Our findings highlight the need for rigorous adjustment for patient risk factors in anesthesia patient safety studies.

SCAI/CCAS/SPA Expert Consensus Statement for Anesthesia and Sedation Practice: Recommendations for Patients Undergoing Diagnostic and Therapeutic Procedures in the Pediatric and Congenital Cardiac Catheterization Laboratory.

Current practice of sedation and anesthesia for patients undergoing pediatric and congenital cardiac catheterization laboratory (PCCCL) procedures is known to vary among institutions, a multi-society expert panel with representatives from the Congenital Heart Disease Council of the Society for Cardiovascular Angiography and Interventions, the Society for Pediatric Anesthesia and the Congenital Cardiac Anesthesia Society was convened to evaluate the types of sedation and personnel necessary for procedures performed in the PCCCL. The goal of this panel was to provide practitioners and institutions performing these procedures with guidance consistent with national standards and to provide clinicians and institutions with consensus-based recommendations and the supporting references to encourage their application in quality improvement programs. Recommendations can neither encompass all clinical circumstances nor replace the judgment of individual clinicians in the management of each patient. The science of medicine is rooted in evidence, and the art of medicine is based on the application of this evidence to the individual patient. This expert consensus statement has adhered to these principles for optimal management of patients requiring sedation and anesthesia. What follows are recommendations for patient monitoring in the PCCCL regardless of whether minimal or no sedation is being used or general anesthesia is being provided by an anesthesiologist.

Patients with single ventricle physiology undergoing noncardiac surgery are at high risk for adverse events.

BACKGROUND: Patients with single ventricle physiology are at increased anesthetic risk when undergoing noncardiac surgery. OBJECTIVE: To review the outcomes of anesthetics for patients with single ventricle physiology undergoing noncardiac surgery. METHODS: This study is a retrospective chart review of all patients who underwent a palliative procedure for single ventricle physiology between January 1, 2007 and January 31, 2014. Anesthetic and surgical records were reviewed for noncardiac operations that required sedation or general anesthesia. Any noncardiac operation occurring prior to completion of a bidirectional Glenn procedure was included. Diagnostic procedures, including cardiac catheterization, insertion of permanent pacemaker, and procedures performed in the ICU, were excluded. RESULTS: During the review period, 417 patients with single ventricle physiology had initial palliation. Of these, 70 patients (16.7%) underwent 102 anesthetics for 121 noncardiac procedures. The noncardiac procedures included line insertion (n = 23); minor surgical procedures such as percutaneous endoscopic gastrostomy or airway surgery (n = 38); or major surgical procedures including intra-abdominal and thoracic operations (n = 41). These interventions occurred on median day 60 of life (1-233 days). The procedures occurred most commonly in the operating room (n = 79, 77.5%). Patients' median weight was 3.4 kg (2.4-15 kg) at time of noncardiac intervention. In 102 anesthetics, 26 patients had an endotracheal tube or tracheostomy in situ, 57 patients underwent endotracheal intubation, and 19 patients had a natural or mask airway. An intravenous induction was performed in 77 anesthetics, an inhalational induction in 17, and a combination technique in 8. The median total anesthetic time was 126 min (14-594 min). In 22 anesthetics (21.6%), patients were on inotropic support upon arrival; an additional 24 patients required inotropic support (23.5%), of which dopamine was the most common medication. There were 10 intraoperative adverse events (9.8%) including: arrhythmias requiring treatment (n = 4), conversion from sedation to a general anesthetic (n = 2), difficult airway (n = 1), inadvertent extubation with desaturation and bradycardia (n = 1), hypotension and desaturation (n = 1), and cardiac arrest (n = 1). Postoperative events (<48 h) included ST segment changes requiring cardiac catheterization (n = 1), and cardiorespiratory arrest (n = 1). Age, size, gender, type of cardiac palliation, patient location, procedure location, and type of procedure were not associated with adverse outcome. After 62 anesthetics (60.8%), patients went postoperatively to the cardiac ICU. There were no deaths at 48 h. CONCLUSION: We observed no mortality during or after noncardiac surgery in a high-risk subgroup of palliated cardiac patients with single ventricle physiology. However, 11.8% of patients had an adverse event associated with their anesthetic.

The frequency of cardiac arrests in patients with congenital heart disease undergoing cardiac catheterization.

BACKGROUND: Cardiac catheterization for patients with congenital heart disease has shifted from diagnostic to predominantly interventional procedures because of advances in catheter-based technologies. Children undergoing therapeutic catheterization may be at higher risk of adverse events, and the purpose of our study was to determine the incidence of cardiac arrest (CA) in patients with congenital heart disease undergoing cardiac catheterization at a large pediatric tertiary referral center. METHODS: All CAs from January 2004 through December 2009 occurring in the cardiac catheterization laboratory were reviewed. A CA was defined as an event in which cessation of circulation required chest compressions. Procedure, patient, practitioner, and system-related factors were examined. RESULTS: Over the study period, during 7289 catheterization procedures, 70 procedures were associated with a CA (0.96 [99% confidence interval, 0.7-1.3] per 100 procedures); 48 events (69%) were successfully resuscitated to a perfusing rhythm, 18 events (26%) resulted in need for extracorporeal membrane oxygenation, and 4 events (6%) resulted in unsuccessful resuscitation. Sudden onset of cardiac arrhythmia led to CA during 38 events (54%). The duration of resuscitation after CA was ≤11 minutes in 71%. Occurrence of CA was associated with interventional procedures (P < 0.001) and younger age (P < 0.001). A change in systems for scheduling and communication of cases was associated with a significant reduction in the incidence of CA (1.5% vs 0.7%; P = 0.002). CONCLUSIONS: The incidence of CA in children undergoing cardiac catheterization is high compared with pediatric noncardiac surgery. Procedural and system factors were associated with occurrence of CA in this cohort. These issues highlight the need for close communication, anticipation, and preparation.

How Should We Care for Patients with Congenital Heart Diseases Undergoing Surgical Procedures in Ambulatory Settings?

Congenital heart diseases (CHDs) are the most common of all congenital birth anomalies. As the survival of patients with CHDs continues to improve, this patient population is presenting for non-cardiac procedures more frequently than in the past. With ambulatory based procedures becoming increasingly common, it is critical to consider how we should best triage these patients for procedures in ambulatory settings. This paper reviews the current literature on the subject and considers strategies to guide future management.

Intubation precautions in a pediatric patient with severe COVID-19.

We present the case of a child diagnosed with COVID-19 soon after open-heart surgery who required an urgent second surgery. The patient suffered from severe COVID-19 disease. The utility of preoperative COVID-19 testing, determination of recovery by an array of inflammatory markers and perioperative management are described.

Hemostatic consequences of a non-fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants.

OBJECTIVES: Despite aggressive measures to miniaturize the cardiopulmonary bypass (CPB) circuit in neonates and infants, the CPB prime volume is often at least as large as the patients' blood volume. We conducted an observational study to characterize the hemostatic consequences of a CPB prime consisting of either non-fresh or reconstituted whole blood. METHODS: Hematocrit, fibrinogen, platelet count, plasminogen, anti-thrombin III (AT-III), and factors (F) II, V, VII, IX, and X of 30 neonates and infants undergoing cardiac surgery with CPB utilizing either a non-fresh or reconstituted whole blood prime were prospectively evaluated at eight time points. Following protamine administration, microvascular bleeding was treated by protocol. RESULTS: The hemostatic composition of the CPB prime was the same following the use of either non-fresh or reconstituted whole blood. The CPB prime platelet count (mean +/- SD) was 5.87 +/- 2.84 x 10(3) microl(-1) when compared to a preoperative platelet count of 298 +/- 142 x 10(3) microl(-1) (P < 0.0001). Twenty patients received 17.3 +/- 9.2 ml x kg(-1) (0.86 +/- 0.46 units x kg(-1)) of platelets with significant improvement in platelet count. Nine patients received 16.7 +/- 13.4 ml x kg(-1) (0.84 +/- 0.67 units x kg(-1)) of cryoprecipitate with significant improvements in FVIII and fibrinogen. CONCLUSIONS: Non-fresh or reconstituted whole blood as a component of a small volume CPB prime in neonates and infants induces clinically significant dilutional thrombocytopenia in conjunction with less significant reductions in fibrinogen, FII, FV, FVII, FVIII, FIX, FX, plasminogen, and AT-III.

Volatile anesthetics affect macrophage phagocytosis.

BACKGROUND: Perioperative infections, particularly surgical site infections pose significant morbidity and mortality. Phagocytosis is a critical step for microbial eradication. We examined the effect of commonly used anesthetics on macrophage phagocytosis and its mechanism. METHODS: The effect of anesthetics (isoflurane, sevoflurane, propofol) on macrophage phagocytosis was tested using RAW264.7 mouse cells, mouse peritoneal macrophages, and THP-1 human cells. Either opsonized sheep erythrocytes or fluorescent labeled Escherichia coli were used as phagocytic objects. The activation of Rap1, a critical protein in phagocytosis was assessed using the active Rap1 pull-down and detection kit. To examine anesthetic binding site(s) on Rap1, photolabeling experiments were performed using azi-isoflurane and azi-sevoflurane. The alanine scanning mutagenesis of Rap1 was performed to assess the role of anesthetic binding site in Rap1 activation and phagocytosis. RESULTS: Macrophage phagocytosis was significantly attenuated by the exposure of isoflurane (50% reduction by 1% isoflurane) and sevoflurane (50% reduction by 1.5% sevoflurane), but not by propofol. Photolabeling experiments showed that sevoflurane directly bound to Rap1. Mutagenesis analysis demonstrated that the sevoflurane binding site affected Rap1 activation and macrophage phagocytosis. CONCLUSIONS: We showed that isoflurane and sevoflurane attenuated macrophage phagocytosis, but propofol did not. Our study showed for the first time that sevoflurane served as a novel small GTPase Rap1 inhibitor. The finding will further enrich our understanding of yet-to-be determined mechanism of volatile anesthetics and their off-target effects. The sevoflurane binding site was located outside the known Rap1 functional sites, indicating the discovery of a new functional site on Rap1 and this site would serve as a pocket for the development of novel Rap1 inhibitors.

Cardiac magnetic resonance versus routine cardiac catheterization before bidirectional glenn anastomosis in infants with functional single ventricle: a prospective randomized trial.

BACKGROUND: Routine preoperative catheterization is standard practice in patients with single-ventricle physiology before bidirectional Glenn anastomosis. Because catheterization is invasive and exposes patients to ionizing radiation, cardiac magnetic resonance (CMR) may be a safe and effective alternative. METHODS AND RESULTS: We conducted a prospective, randomized, single-center clinical trial comparing catheterization with CMR in patients considered for bidirectional Glenn operation from February 2003 to June 2006. End points were frequency of adverse events of the preoperative evaluation and a composite score of clinically successful surgery. Of 92 eligible patients, 82 were enrolled on the basis of screening echocardiogram, fulfillment of inclusion criteria, and informed consent. Patients were randomized to catheterization (n=41) or CMR (n=41). There were no baseline differences between groups. Four treatment crossovers occurred, 3 to catheterization and 1 to CMR. Catheter interventions were performed in 17 patients (41%). Catheterization resulted in more minor adverse events (78% versus 5%; P<0.001), longer preoperative hospital stays (median, 2 versus 1 day; P<0.001), and higher hospital charges ($34 477 versus $14 921; P<0.001). There was 1 major adverse event in the CMR group (P=1.0). The operative course and frequency of postoperative complications were similar between the 2 groups. The proportion of patients who had a successful bidirectional Glenn operation was similar (71% versus 83%; P=0.3). At the 3-month follow-up, there were no differences in clinical status, oxygen saturation, or frequency of reinterventions. CONCLUSIONS: CMR is a safe, effective, and less costly alternative to routine catheterization in the evaluation of selected patients before bidirectional Glenn operation. Further studies are necessary to determine whether there are long-term benefits from transcatheter interventions in these patients.

Trendelenburg position, simulated Valsalva maneuver, and liver compression do not alter the size of the right internal jugular vein in patients with a bidirectional Glenn shunt.

BACKGROUND: Ultrasound is increasingly used to facilitate right internal jugular vein (RIJV) cannulation in children. In children without cardiac disease, position changes and enhancement maneuvers increase RIJV cross-sectional area (CSA) and further facilitate cannulation. We investigated the effect of these maneuvers on RIJV CSA in children with a bidirectional Glenn (BDG) shunt presenting for a Fontan procedure. METHODS: The CSA (cm(2)) of the RIJV in 21 children with a BDG shunt presenting for a Fontan procedure was assessed by ultrasonic planimetry (SonoSite). Two positions, supine (S) and 15 degrees Trendelenburg (T); and two enhancements maneuvers, manual liver compression (L) and a simulated Valsalva maneuver (V) were utilized in combination. Eight separate measurements (S, S + L, S + V, S + L + V, T, T + L, T + V, T + L + V) were made in each patient. Data were analyzed using one-way analysis of variance with repeated measures and with Tukey post hoc pairwise comparison analysis. RESULTS: No significant change in the RIJV CSA or % change in CSA from baseline (S) was observed. CONCLUSIONS: Position changes and enhancement maneuvers are unlikely to facilitate RIJV cannulation in BDG shunt patients presenting for Fontan procedure because these interventions do not increase RIJV CSA.

The frequency of anesthesia-related cardiac arrests in patients with congenital heart disease undergoing cardiac surgery.

BACKGROUND: The frequency of anesthesia-related cardiac arrests during pediatric anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA physical status >III and younger age are risk factors. Patients with congenital cardiac disease may also be at increased risk. Therefore, in this study, we evaluated the frequency of cardiac arrest in patients with congenital heart disease undergoing cardiac surgery at a large pediatric tertiary referral center. METHODS: Using an established data registry, all cardiac arrests from January 2000 through December 2005 occurring in the cardiac operating rooms were reviewed. A cardiac arrest was defined as any event requiring external or internal chest compressions, with or without direct cardioversion. Events determined to be anesthesia-related were classified as likely related or possibly related. RESULTS: There were 41 cardiac arrests in 40 patients (median age, 2.9 mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no mortality; 30 were categorized as procedure-related. The incidence of anesthesia-related and procedure-related cardiac arrests was highest in neonates (P < 0.001). There was no association with year of event or experience of the anesthesiologist. CONCLUSION: The frequency of anesthesia-related cardiac arrest in patients undergoing cardiac surgery is increased, but is not associated with an increase in mortality. Neonates and infants are at higher risk. Careful preparation and anticipation is important to ensure timely and effective resuscitation.