Clinical Trials
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The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
Not Recruiting
The purpose of this study is to assess whether the type of anesthesia, narcotic-based versus inhalational anesthesia administered during cardiopulmonary bypass (CPB) surgery contributes to the wide variation in neurologic recovery and developmental outcome after surgery in infants with congenital heart disease.
Stanford is currently not accepting patients for this trial.
All Publications
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Balloon Angioplasty for Pulmonary Artery Stenosis After Complete Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals
JOURNAL OF INVASIVE CARDIOLOGY
2021; 33 (5): E378-E386
View details for Web of Science ID 000648791300008
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Balloon Angioplasty for Pulmonary Artery Stenosis After Complete Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals.
The Journal of invasive cardiology
2021
Abstract
OBJECTIVES: The objective of this study was to assess procedural outcomes of balloon pulmonary artery (PA) angioplasty procedures after complete repair of tetralogy of Fallot with major aortopulmonary collateral arteries (TOF/MAPCAs).BACKGROUND: Our approach to patients with TOF/MAPCAs emphasizes early complete unifocalization and repair. Major PA reinterventions are relatively uncommon. Balloon PA angioplasty is often used, but the effectiveness of balloon PA angioplasty in this population is unknown.METHODS: The study cohort comprised patients who underwent complete unifocalization and repair of TOF/ MAPCAs at our center between 2002-2018 and underwent balloon PA angioplasty after repair. To assess immediate procedural outcomes, pre- and postintervention PA measurements were compared.RESULTS: We reviewed 134 vessels that were dilated a median of 1.1 years after repair in 60 patients (median 2 PA branches per patient). Treated vessels included 15 central, 64 lobar, and 55 segmental branches. The median PA diameter at the level of stenosis increased from 1.9 mm to 3.3 mm (P<.001), and the median diameter increase was 50%. All but 6 treated vessels were enlarged. The stenosis-distal diameter ratio increased from a median of 64% to 89% (P<.001). The median central PA to aortic systolic pressure ratio was 47% before and 39% after intervention (P<.001).CONCLUSIONS: Balloon PA angioplasty was acutely effective at treating most stenoses of reconstructed PA branches after repair of TOF/MAPCAs. Simple angioplasty can be a useful tool in treating isolated or modest stenoses after unifocalization/PA reconstruction surgery using our approach.
View details for PubMedID 33908895
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Mid-Term Outcomes After Unifocalization Guided by Intraoperative Pulmonary Flow Study.
World journal for pediatric & congenital heart surgery
2021; 12 (1): 76–83
Abstract
BACKGROUND: Repair of tetralogy of Fallot (TOF) with major aortopulmonary collateral arteries (MAPCAs) requires unifocalization of pulmonary circulation, intracardiac repair with the closure of the ventricular septal defect, and placement of a right ventricle (RV) to pulmonary artery (PA) conduit. The decision to perform complete repair is sometimes aided by an intraoperative flow study to estimate the total resistance of the reconstructed pulmonary circulation.METHODS: We reviewed patients who underwent unifocalization and PA reconstruction for TOF/MAPCAs to evaluate acute and mid-term outcomes after repair with and without flow studies and to characterize the relationship between PA pressure during the flow study and postrepair RV pressure.RESULTS: Among 579 patients who underwent unifocalization and PA reconstruction for TOF/MAPCAs, 99 (17%) had an intraoperative flow study during one (n = 91) or more (n = 8) operations to determine the suitability for a complete repair. There was a reasonably good correlation between mean PA pressure at 3 L/min/m2 during the flow study and postrepair RV pressure and RV:aortic pressure ratio. Acute and mid-term outcomes (median: 3.8 years) after complete repair in the flow study patients (n = 78) did not differ significantly from those in whom the flow study was not performed (n = 444). Furthermore, prior failed flow study was not associated with differences in outcome after subsequent intracardiac repair.CONCLUSIONS: The intraoperative flow study remains a useful adjunct for determining the suitability for complete repair in a subset of patients undergoing surgery for TOF/MAPCAs, as it is reasonably accurate for estimating postoperative PA pressure and serves as a reliable guide for the feasibility of single-stage complete repair.
View details for DOI 10.1177/2150135120964427
View details for PubMedID 33407027
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Longevity of large aortic allograft conduits in Tetralogy with major aortopulmonary collaterals.
The Annals of thoracic surgery
2021
Abstract
Appropriate conduit selection for right ventricle (RV) to pulmonary artery (PA) connection has been extensively studied, with older implantation age, pulmonary (v. aortic) homografts, and true-sizing associated with increased longevity. Notably, patients with PA arborization abnormalities (ie MAPCAs) are reported to require earlier and more frequent conduit interventions. We aim to understand the behavior of large diameter aortic homografts in patients with MAPCAs, which are programmatically utilized at our institution.This is a single-center retrospective cohort study including all children < 12 years of age who underwent RV-PA connection using an aortic homograft ≥ 16mm diameter between 2002-2019, with a primary outcome of freedom from any RV-PA reintervention and a secondary outcome of freedom from surgical reintervention. Patients were grouped by absolute and indexed conduit sizes for further analysis.A total of 336 conduits were followed for a median of 3.0 years; transcatheter (n = 30) and/or surgical (n = 35) reintervention was performed on 64 conduits. Estimated freedom from reintervention and surgical replacement was 84% and 90% at 5 years. Younger age and smaller absolute conduit size were associated with earlier reintervention, but conduit z-score (median 3.5) was not assocated with outcome.The programmatic use of oversized aortic homograft RV-PA conduits in the surgical repair of MAPCAs provides a focused experience that demonstrates similar longevity to reported best alternatives. Secondarily, conduit oversizing may improve durability and enables an increased likelihood of non-operative reintervention.
View details for DOI 10.1016/j.athoracsur.2021.01.054
View details for PubMedID 33600790
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Outcomes in Patients with Alagille Syndrome and Complex Pulmonary Artery Disease.
The Journal of pediatrics
2020
Abstract
To assess outcomes in a large cohort of patients with Alagille Syndrome (ALGS) who underwent pulmonary artery reconstruction surgery for complex PA disease.Patients with ALGS who underwent PA reconstruction surgery at Lucile Packard Children's Hospital Stanford were reviewed. Patients were examined as an overall cohort and based on the primary cardiovascular diagnosis: severe isolated branch PA stenosis, tetralogy of Fallot (TOF) without major aortopulmonary collateral arteries (MAPCAs), or TOF with MAPCAs RESULTS: Fifty-one patients with ALGS underwent PA surgery at our center: 22 with severe branch PA stenosis, 9 with TOF without MAPCAs, and 20 with TOF and MAPCAs. Forty-one patients (80%) achieved a complete repair. Five of the patients with TOF with MAPCAs (25%) had a complete repair at the first surgery, compared with 8 (89%) and 19 (86%) with TOF without MAPCAs and isolated branch PA stenosis, respectively. At a median follow-up of 1.7 years after the first surgery, 39 patients (76%) were alive, 36 with a complete repair and a median PA:aortic systolic pressure ratio of 0.38. Nine patients (18%), 8 with isolated branch PA stenosis, underwent liver transplantation.Most patients with ALGS and complex PA disease can undergo complete repair with low postoperative right ventricular pressure. Patients with TOF/MAPCAs had the worst outcome, with higher mortality and more frequent PA interventions compared with patients with TOF without MAPCAs or isolated branch PA stenosis. Complex PA disease is not a contraindication to liver transplantation in patients with ALGS.
View details for DOI 10.1016/j.jpeds.2020.09.053
View details for PubMedID 32980376
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The Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons Cardiac Anesthesia Database Collaboration.
World journal for pediatric & congenital heart surgery
2020; 11 (1): 14–21
Abstract
Multi-institutional databases and registries have proliferated over the last decade in all specialties of medicine. They may be especially helpful in low-frequency/high-acuity fields such as pediatric and congenital heart diseases. The Society of Thoracic Surgeon's Congenital Heart Surgery Database (STSCHSD) is the largest single data set for the congenital heart disease population and includes contemporaneous data from over 120 programs in the United States (and several outside of the United States), capturing greater than 98% of the congenital cardiac surgical procedures in the United States. In 2010, the Congenital Cardiac Anesthesia Society partnered with the STSCHSD to incorporate anesthesia-related elements into the data set. Voluntary site participation in the anesthesia data has grown steadily. Currently, over 60 sites performing more than 60% of cardiac bypass procedures in the STSCHSD are submitting anesthesia data annually into the STSCHSD. Anesthesia data include perioperative medication usage, modalities for hemodynamic and neurologic monitoring, blood product, antifibrinolytic and procoagulant use, and anesthesia-related adverse events. This special article provides a descriptive summary of relevant findings to date, reflecting the wide variety in anesthesia practice patterns present among institutions and illustrates the functionality of a multisite registry in pediatric cardiac anesthesia which can be utilized both locally and nationally.
View details for DOI 10.1177/2150135119884911
View details for PubMedID 31835986
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Platelet Administration During Cardiopulmonary Bypass in Neonates: A Universal Therapy Applied in a Novel Way.
World journal for pediatric & congenital heart surgery
2020; 11 (1): 77–78
Abstract
Advances in pharmaceuticals (eg, factor concentrates), laboratory testing (eg, rotational thromboelastometry), and processes (eg, transfusion protocols) have contributed to improved outcomes regarding transfusion in neonates undergoing surgical repair for congenital heart disease. A novel strategy, platelets administered during the rewarming phase of cardiopulmonary bypass, as a solution to improved hemostasis, was prospectively evaluated in 42 neonates. Improved intraoperative and postoperative hemostasis was observed in neonates given platelets during the rewarming phase of cardiopulmonary bypass.
View details for DOI 10.1177/2150135119890248
View details for PubMedID 31835980
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Transfusion Outcomes in Patients Undergoing Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals.
World journal for pediatric & congenital heart surgery
2020; 11 (2): 159–65
Abstract
Surgical repair of tetralogy of Fallot and major aortopulmonary collaterals (TOF/MAPCAs) involves unifocalization of MAPCAs and reconstruction of the pulmonary arterial circulation. Surgical and cardiopulmonary bypass (CPB) times are long and suture lines are extensive. Maintaining patency of the newly anastomosed vessels while achieving hemostasis is important, and assessment of transfusion practices is critical to successful outcomes.Clinical, surgical, and transfusion data in patients with TOF/MAPCAs repaired at our institution (2013-2018) were reviewed. Types and volumes of blood products used in the perioperative period, in addition to the use of antifibrinolytics and/or procoagulants (factor VIII inhibitor bypassing activity [FEIBA]; anti-inhibitor coagulant complex), were assessed. Outcome measures included days on mechanical ventilation (DOMV), postoperative intensive care unit and hospital length of stay (LoS), and incidence of thrombosis.Perioperative transfusion data from 279 patients were analyzed. Surgical (879 ± 175 minutes vs 684 ± 257 minutes) and CPB times (376 ± 124 minutes vs 234 ± 122 minutes) were longer in patients who received FEIBA than those who did not. Although the indexed volume of packed red blood cells (128.4 ± 82.2 mL/kg) and fresh frozen plasma (64.2 ± 41.1 mL/kg) was similar in patients who did and did not receive FEIBA, the amounts of cryoprecipitate (5.5 ± 5.2 mL/kg vs 5.8 ± 4.8 mL/kg) and platelets (19.5 ± 20.7 mL/kg vs 20.8 ± 13 mL/kg) transfused were more in those who did receive FEIBA.Perioperative transfusion is an important component in the overall surgical and anesthetic management of patients with TOF/MAPCAs. The intraoperative use of FEIBA was not associated with a decrease in the amount of blood products transfused, DOMV, or LoS or with an increase in thrombotic complications.
View details for DOI 10.1177/2150135119892192
View details for PubMedID 32093560
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Unifocalization and pulmonary artery reconstruction in patients with tetralogy of Fallot and major aortopulmonary collateral arteries who underwent surgery before referral.
The Journal of thoracic and cardiovascular surgery
2020
Abstract
The study objective was to characterize and analyze outcomes in patients with tetralogy of Fallot and major aortopulmonary collateral arteries who had undergone surgery elsewhere before referral (prereferral surgery).Patients with tetralogy of Fallot and major aortopulmonary collateral arteries who underwent surgery between 2001 and 2019 at our center were reviewed. Prereferral surgery and unoperated patients were compared, as were subsets of prereferral surgery patients who had undergone different types of prior procedures. Primary outcomes included complete repair with survival to 6 months, death, and perioperative metrics.Of 576 patients studied, 200 (35%) had undergone a wide range and number of prior operations elsewhere, including 92 who had pulmonary blood supply through a shunt and 108 who had a right ventricle pulmonary artery connection. Patients who underwent prereferral surgery with an existing right ventricle pulmonary artery connection had undergone more prereferral surgery procedures than those with a shunt and were more likely to have a right ventricle outflow tract pseudoaneurysm or pulmonary artery stent (all P < .001) at the time of referral. The cumulative incidences of complete repair and death were similar regardless of prereferral surgery status, but the cumulative incidence of complete repair with 6-month survival was higher (P = .002) and of death lower (P = .18) in patients who had prior right ventricle pulmonary artery connection compared with those who had received a prior shunt only.Our comprehensive management strategy for tetralogy of Fallot and major aortopulmonary collateral arteries can be applied with excellent procedural results in both unoperated patients and those who have undergone multiple and varied procedures elsewhere.
View details for DOI 10.1016/j.jtcvs.2020.03.062
View details for PubMedID 32444187
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Outcomes After Aortopulmonary Window for Hypoplastic Pulmonary Arteries and Dual-Supply Collaterals
ANNALS OF THORACIC SURGERY
2019; 108 (3): 820–27
View details for DOI 10.1016/j.athoracsur.2019.03.022
View details for Web of Science ID 000482187400054
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Assessment of the Reconstructed Pulmonary Circulation With Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals
WORLD JOURNAL FOR PEDIATRIC AND CONGENITAL HEART SURGERY
2019; 10 (3): 313–20
View details for DOI 10.1177/2150135119836735
View details for Web of Science ID 000470668700010
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Preoperative Laboratory Studies for Pediatric Cardiac Surgery Patients: A Multi-Institutional Perspective
ANESTHESIA AND ANALGESIA
2019; 128 (5): 1051–54
View details for DOI 10.1213/ANE.0000000000004114
View details for Web of Science ID 000480723100038
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Tetralogy of Fallot: Everything you wanted to know but were afraid to ask
PEDIATRIC ANESTHESIA
2019; 29 (5): 475–82
View details for DOI 10.1111/pan.13569
View details for Web of Science ID 000468217100012
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Outcomes After Aortopulmonary Window for Hypoplastic Pulmonary Arteries and Dual-Supply Collaterals.
The Annals of thoracic surgery
2019
Abstract
BACKGROUND: Our institutional approach to tetralogy of Fallot (TOF) with major aortopulmonary collateral arteries (MAPCAs) emphasizes early unifocalization and complete repair (CR). In the small subset of patients with dual-supply MAPCAs and confluent but hypoplastic central pulmonary arteries (PAs), our surgical approach is early creation of an aortopulmonary window (APW) to promote PA growth. Factors associated with successful progression to CR, and mid-term outcomes have not been assessed.METHODS: Clinical data were reviewed. PA diameters were measured off-line from angiograms prior to APW and on follow-up catheterization >1 month after APW but prior to any additional surgical interventions.RESULTS: From 11/01-3/18, 352 patients with TOF/MAPCAs underwent initial surgery at our center, 40 of whom had a simple APW with or without ligation of MAPCAs as the first procedure (median age 1.4 months). All PA diameters increased significantly on follow-up angiography. Ultimately, 35 patients underwent CR after APW. Nine of these patients (26%) underwent intermediate palliative operation between 5 and 39 months (median 8 months). There were no early deaths. The cumulative incidence of CR was 65% 1 year post-APW and 87% at 3 years. Repaired patients were followed for a median of 4.2 years after repair; the median PA:aortic pressure ratio was 0.39 (0.22-0.74).CONCLUSIONS: Most patients with TOF/MAPCAs and hypoplastic but normally arborizing PAs and dual-supply MAPCAs are able to undergo CR with low right ventricular pressure after APW early in life. Long-term outcomes were good, with acceptable PA pressures in most patients.
View details for PubMedID 30980823
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Repair of Untreated Older Patients With Tetralogy of Fallot With Major Aortopulmonary Collaterals
ANNALS OF THORACIC SURGERY
2019; 107 (4): 1218–25
View details for DOI 10.1016/j.athoracsur.2018.11.016
View details for Web of Science ID 000462308000055
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A Prospective Assessment of Optimal Mechanical Ventilation Parameters for Pediatric Catheter Ablation
PEDIATRIC CARDIOLOGY
2019; 40 (1): 126–32
Abstract
Catheter stability, an important factor in ablation success, is affected by ventilation. Optimal ventilation strategies for pediatric catheter ablation are not known. We hypothesized that small tidal volume and positive end-expiratory pressure are associated with reduced ablation catheter movement at annular positions. Subjects aged 5-25 years undergoing ablation for supraventricular tachycardia (SVT) or WPW at two centers from March 2015 to September 2016 were prospectively enrolled and randomized to receive mechanical ventilation with either positive end-expiratory pressure of 5 cm H2O (PEEP) or 0 cm H2O (ZEEP). Movement of the ablation catheter tip at standard annular positions was measured using 3D electroanatomic mapping systems under two conditions: small tidal volume (STV) (3-5 mL/kg) or large TV (LTV) (6-8 mL/kg). 58 subjects (mean age 13.8 years) were enrolled for a total of 266 separate observations of catheter movement. STV ventilation was associated with significantly reduced catheter movement, compared to LTV at all positions (right posteroseptal: 2.5 ± 1.4 vs. 5.2 ± 3.1 mm, p < 0.0001; right lateral: 2.7 ± 1.6 vs. 6.3 ± 3.5 mm, p < 0.0001; left lateral: 1.8 ± 1.0 vs. 4.3 ± 1.9 mm, p < 0.0001). The presence or absence of PEEP had no effect on catheter movement. In multivariable analysis, STV was associated with a 3.1-mm reduction in movement (95% CI 2.6-3.5, p < 0.0001), adjusting for end-expiratory pressure, annular location, and patient size. We conclude that STV ventilation is associated with reduced ablation catheter movement compared to a LTV strategy, independent of PEEP and annular position.
View details for PubMedID 30178187
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Pulmonary hemorrhage in children with Alagille syndrome undergoing cardiac catheterization.
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions
2019
Abstract
To evaluate the incidence, severity, and outcomes of pulmonary hemorrhage in children with Alagille syndrome (AGS) undergoing cardiac catheterization, and to find variables associated with hemorrhage in this population.Children with AGS have a high incidence of bleeding complications during invasive procedures. It has been our impression that catheterization-associated pulmonary hemorrhage is more common in children with AGS, but there are no published data on this topic.This was a retrospective single institution study of children with AGS undergoing catheterization from 2010 to 2018. Pulmonary hemorrhage was defined as angiographic or fluoroscopic evidence of extravasated blood in the lung parenchyma, or blood suctioned from the endotracheal tube with documentation of pulmonary hemorrhage by the anesthesiologist or intensivist. Univariate comparisons were made between catheterizations that did and did not have pulmonary hemorrhage.Thirty children with AGS underwent 87 catheterizations, 32 (37%) with interventions on the branch pulmonary arteries (PA). There were 26 (30%) procedures with hemorrhage, the majority (65%) of which were self-limited or required less than 24 hr of mechanical ventilation. Moderate and severe hemorrhage occurred only in children with tetralogy of Fallot (TOF; 5 of 14, 36%). A higher right ventricle to aorta systolic pressure ratio (1.0 [0.85-1.1] vs. 0.88 [0.59-1.0], p = .029) and interventions on the branch PAs (14 of 26, 54% vs. 18 of 61, 30%, p = .032) were associated with hemorrhage.Pulmonary hemorrhage was common in children with AGS undergoing both intervention and diagnostic cardiac catheterization, and was associated with TOF, higher RV to aorta pressure ratio, and interventions on the branch PAs.
View details for DOI 10.1002/ccd.28508
View details for PubMedID 31584246
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Assessment of airway abnormalities in patients with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals.
Cardiology in the young
2019: 1–5
Abstract
Children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals (TOF/MAPCAs) are at risk for post-operative respiratory complications after undergoing unifocalisation surgery. Thus, we assessed and further defined the incidence of airway abnormalities in our series of over 500 children with TOF/MAPCAs as determined by direct laryngoscopy, chest computed tomography (CT), and/or bronchoscopy.The medical records of all patients with TOF/MAPCAs who underwent unifocalisation or pulmonary artery reconstruction surgery from March, 2002 to June, 2018 were reviewed. Anaesthesia records, peri-operative bronchoscopy, and/or chest CT reports were reviewed to assess for diagnoses of abnormal or difficult airway. Associations between chromosomal anomalies and airway abnormalities - difficult anaesthetic airway, bronchoscopy, and/or CT findings - were defined.Of the 564 patients with TOF/MAPCAs who underwent unifocalisation or pulmonary artery reconstruction surgery at our institution, 211 (37%) had a documented chromosome 22q11 microdeletion and 28 (5%) had a difficult airway/intubation reported at the time of surgery. Chest CT and/or peri-operative bronchoscopy were performed in 234 (41%) of these patients. Abnormalities related to malacia or compression were common. In total 35 patients had both CT and bronchoscopy within 3 months of each other, with concordant findings in 32 (91%) and partially concordant findings in the other 3.This is the largest series of detailed airway findings (direct laryngoscopy, CT, and bronchoscopy) in TOF/MAPCAS patients. Although these findings are specific to an at-risk population for airway abnormalities, they support the utility of CT and /or bronchoscopy in detecting airway abnormalities in patients with TOF/MAPCAs.
View details for PubMedID 31044684
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Deletion of 22q11 chromosome is associated with postoperative morbidity after unifocalisation surgery
CARDIOLOGY IN THE YOUNG
2019; 29 (1): 19–22
View details for DOI 10.1017/S1047951118001427
View details for Web of Science ID 000454076300004
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Outcomes After Initial Unifocalization to a Shunt in Complex Tetralogy of Fallot with MAPCAs.
The Annals of thoracic surgery
2019
Abstract
Our approach to tetralogy of Fallot (TOF) with pulmonary atresia and major aortopulmonary collateral arteries (MAPCAs) emphasizes early single-stage unifocalization and intracardiac repair. However, a subset of patients with small native pulmonary arteries (PAs) and MAPCAs undergo unifocalization to a shunt rather than simultaneous intracardiac repair.Patients with TOF/MAPCAs who underwent unifocalization to a systemic-to-PA shunt by a single surgeon were reviewed. The decision to perform simultaneous intracardiac repair was based on an intraoperative flow study or empirical assessment of PA and MAPCA size.From 11/01-12/17, 57 patients with TOF/MAPCAs underwent unifocalization to a shunt at a median age of 6.9 months. Genetic abnormalities were documented in 60% of patients, including a chromosome 22q11 deletion in 25 and Alagille syndrome in 8. Twenty patients (35%) had undergone prior surgery elsewhere (n=16) and/or at our center (n=7). During a median follow-up of 5.4 years, 9 patients had additional surgery to revise the PA reconstruction before complete repair, and 38 patients underwent complete repair. Survival was 74±6% 5 years after unifocalization. At follow-up, the median PA:aortic systolic pressure ratio was 0.36 and was >0.50 in 2 patients.In patients with the smallest MAPCAs and PAs, single-stage unifocalization to a shunt followed by intracardiac repair yields an excellent outcome in most cases.
View details for DOI 10.1016/j.athoracsur.2019.01.030
View details for PubMedID 30772338
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Tetralogy of Fallot: Everything You Wanted to Know butWere Afraid to Ask.
Paediatric anaesthesia
2018
Abstract
Tetralogy of Fallot (TOF) is the most common form of congenital cyanotic heart disease, occurring in approximately 4 to 5 per 10,0000 live births, and represents 7-10% of all congenital heart defects (1,2). Although TOF is often thought of in terms of the tetrad of anomalies-pulmonary stenosis, ventricular septal defect (VSD), aorta overriding the ventricular septum, and right ventricular hypertrophy-it has been proposed that all of these features are the result of anterior malalignment of the infundibular septum with the muscular septum (3,4). There are several variants of TOF as well, which manifest other abnormal features and are discussed in the following review. This article is protected by copyright. All rights reserved.
View details for PubMedID 30592107
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Repair of Untreated Older Patients with Tetralogy of Fallot with Major Aortopulmonary Collaterals.
The Annals of thoracic surgery
2018
Abstract
BACKGROUND: Our programmatic approach to tetralogy of Fallot with major aortopulmonary collaterals emphasizes single-stage unifocalization with complete intracardiac repair during infancy. Little is known about suitability for complete repair in patients beyond infancy. We sought to analyze outcomes of our approach in older patients with previously untreated tetralogy of Fallot with major aortopulmonary collaterals.METHODS: Any patient with this lesion not treated prior to 2 years of age referred to our center from 2002-17 met inclusion criteria.RESULTS: Of 33 patients, 32 were out-of-state (64% international) referrals, and 33% (n=11) were >9 years old, had polycythemia, and/or at least 1 high pressure collateral (>25 mm Hg). Complete repair was achieved in 94% (n=31) of patients, 82% (n=27) in one stage and 12% (n=4) after unifocalization to a central shunt. The median right ventricular to aortic pressure ratio was 0.31 after surgery and 0.37 at follow-up. At a median of 4.8 years after repair, 9 patients (19%) underwent reintervention, including 5 conduit and 7 branch pulmonary artery interventions. Three patients also underwent aortic valve replacement.CONCLUSIONS: In this selected cohort of older patients with previously unoperated tetralogy of Fallot with major aortopulmonary collaterals, outcomes were comparable to infants undergoing treatment according to our approach. These findings support the notion that patients who are either born in low-resource settings or present to healthcare providers beyond infancy should be considered candidates and evaluated for complete repair.
View details for PubMedID 30550802
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Deletion of 22q11 chromosome is associated with postoperative morbidity after unifocalisation surgery - CORRIGENDUM.
Cardiology in the young
2018: 1
View details for DOI 10.1017/S1047951118001804
View details for PubMedID 30370896
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Surgical algorithm and results for repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2018; 156 (3): 1194–1204
View details for DOI 10.1016/j.jtcvs.2018.03.153
View details for Web of Science ID 000441556000075
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Deletion of 22q11 chromosome is associated with postoperative morbidity after unifocalisation surgery.
Cardiology in the young
2018: 1–4
Abstract
BACKGROUND: A 22q11 chromosome deletion is common in patients with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals. We sought to determine whether 22q11 chromosome deletion is associated with increased postoperative morbidity after unifocalisation surgery.METHODS: We included all patients with this diagnosis undergoing primary or revision unifocalisation ± ventricular septal defect closure at our institution from 2008 to 2016, and we excluded patients with unknown 22q11 status. Demographic and surgical data were collected. We compared outcomes between those with 22q11 chromosome deletion and those without using non-parametric analysis.RESULTS: We included 180 patients, 41% of whom were documented to have a chromosome 22q11 deletion. Complete unifocalisation was performed in all patients, and intracardiac repair was performed with similar frequency regardless of 22q11 chromosome status. Duration of mechanical ventilation was longer in 22q11 deletion patients. This difference remained significant after adjustment for delayed sternal closure and/or intracardiac repair. Duration of ICU stay was longer in patients with 22q11 deletion, although no longer significant when adjusted for delayed sternal closure and intracardiac repair. Finally, length of hospital stay was longer in 22q11-deleted patients, but this difference was not significant on unadjusted or adjusted analysis.CONCLUSION: Children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals and 22q11 deletion are at risk for greater prolonged mechanical ventilation after unifocalisation surgery. Careful attention should be given to the co-morbidities of this population in the perioperative period to mitigate risks that may complicate the postoperative course.
View details for PubMedID 30160647
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Safety of ferumoxytol in children undergoing cardiac MRI under general anaesthesia.
Cardiology in the young
2018; 28 (7): 916–21
Abstract
BACKGROUND: Ferumoxytol, an "off-label" contrast agent, allows for better cardiac MRI quality as compared with gadolinium-based contrast agents. However, hypotension has been reported with the use of ferumoxytol for indications other than cardiac MRI. The purpose of our investigation was to evaluate the safety of ferumoxytol in children undergoing general anaesthesia for cardiac MRI.METHODS: Medical records of children undergoing general anaesthesia for cardiac MRI were reviewed. Baseline demographic and medical characteristics, as well as imaging and anaesthetic duration and technique, were collected. The incidence of hypotension or other adverse events', need for vasoactive support, or airway intervention throughout the anaesthetic, was recorded.RESULTS: A total of 95 patients were identified, 61 received ferumoxytol and 34 received gadolinium. There were no significant differences between groups with respect to age, weight, or baseline blood pressure. The incidence of low blood pressure - systolic or mean - after contrast administration did not differ between groups, and there was no difference in sustained hypotension or use of vasopressors between groups. One patient who received ferumoxytol had possible anaphylaxis. The image acquisition time (45 versus 68 min, p=0.002) and anaesthesia duration (100 versus 132 min, p=0.02) were shorter in the ferumoxytol group.CONCLUSION: Transient low blood pressure was common in children undergoing cardiac MRI with anaesthesia, but the incidence of hypotension did not differ between ferumoxytol and gadolinium groups. The use of ferumoxytol was associated with significantly shorter scan time and anaesthesia duration, as well as a decreased need for airway intervention.
View details for PubMedID 29848399
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Safety of ferumoxytol in children undergoing cardiac MRI under general anaesthesia
CARDIOLOGY IN THE YOUNG
2018; 28 (7): 916–21
View details for DOI 10.1017/S1047951118000306
View details for Web of Science ID 000434245900004
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An unexpected case of post-operative superior caval vein syndrome.
Cardiology in the young
2018; 28 (6): 879–81
Abstract
Superior caval vein obstruction in children after congenital heart surgery has been more associated with thrombosis formation as result of single-ventricle palliation, infection, indwelling devices/catheters, or external compression. Many of these patients will present to the cardiac catheterisation laboratory for evaluation and possible intervention. We present an unusual case of superior caval vein obstruction in a patient after Tetralogy of Fallot repair.
View details for PubMedID 29697045
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An unexpected case of post-operative superior caval vein syndrome
CARDIOLOGY IN THE YOUNG
2018; 28 (6): 879–81
View details for DOI 10.1017/S1047951118000227
View details for Web of Science ID 000434250000016
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Surgical algorithm and results for repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals.
The Journal of thoracic and cardiovascular surgery
2018
Abstract
OBJECTIVE: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is a complex and heterogeneous form of congenital heart disease. There is a controversy regarding the optimal treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. The purpose of this study was to summarize our algorithm and surgical results for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.METHODS: This was a retrospective review of 307 patients undergoing primary surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Excluded from this analysis were patients who had undergone prior surgical treatment at another institution and patients with single ventricle and major aortopulmonary collateral arteries. There were 3 surgical pathways, including midline unifocalization (n=241), creation of an aortopulmonary window (n=46), and other (n=20).RESULTS: For the 241 patients who underwent midline unifocalization, 204 (85.4%) had a single-stage complete repair. There were 37 patients who underwent a midline unifocalization and central shunt, and 24 have subsequently undergone complete repair. Forty-six patients underwent an aortopulmonary window, of whom 36 have subsequently had a complete repair. There were 20 patients who had complex anatomy and underwent procedures other than described, and14 have subsequently undergone complete repair. Thus, for the patients currently eligible, 280 (93.0%) have achieved complete repair. For the 204 patients who had a single-stage complete repair, the mean right ventricle to aortic pressure ratio was 0.36±0.09. Seventy-six patients underwent a staged repair, and the mean right ventricle to aortic pressure ratio was 0.40±0.09 (P<.05 compared with single-stage repair). There were 3 (1.5%) early and 8 (4.0%) late deaths for the single-stage complete repair cohort versus 4 (4.0%) early and 15 (14.9%) late deaths for all other procedures (P<.01).CONCLUSIONS: The data demonstrate that more than 90% of patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries achieved complete repair. The overall mortality was significantly lower in the subgroup of patients who underwent single-stage complete repair.
View details for PubMedID 29789151
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Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2018; 155 (4): 1747-+
Abstract
Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling.This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed.On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn.In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function.
View details for PubMedID 29223842
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Pulmonary reinterventions after complete unifocalization and repair in infants and young children with tetralogy of Fallot with major aortopulmonary collaterals
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2018; 155 (4): 1696–1707
Abstract
Our institutional approach to tetralogy of Fallot (TOF) with major aortopulmonary collaterals (MAPCAs) emphasizes unifocalization and augmentation of the reconstructed pulmonary arterial (PA) circulation and complete intracardiac repair in infancy, usually in a single procedure. This approach yields a high rate of complete repair with excellent survival and low right ventricular (RV) pressure. However, little is known about remodeling of the unifocalized and reconstructed pulmonary circulation or about reinterventions on the reconstructed PAs or the RV outflow tract conduit.We reviewed patients who underwent complete repair of TOF with MAPCAs at our center at <2 years of age, either as a single-stage procedure or after previous procedures. Outcomes included freedom from conduit or PA intervention after repair, which were assessed by Cox regression and Kaplan-Meier analysis.The study cohort included 272 patients. There were 6 early deaths and a median of follow-up of 3.6 years after complete repair. Reinterventions on the pulmonary circulation were performed in 134 patients, including conduit interventions in 101 patients, branch PA interventions in 101, and closure of residual MAPCAs in 9. The first conduit reintervention consisted of surgical conduit replacement in 77 patients, transcatheter pulmonary valve replacement with a Melody valve in 14, and angioplasty or bare metal stenting in 10. Surgical PA reinterventions were performed in 46 patients and transcatheter reinterventions in 75 (both in 20). Most PA reinterventions involved a single lung, and most transcatheter reinterventions a single vessel. Freedom from conduit replacement or transcatheter pulmonary valve replacement was 70 ± 3% at 5 years and was shorter in patients with smaller initial conduit size. Freedom from any PA reintervention was 64 ± 3% at 5 years, with the greatest rate during the first year. On multivariable analysis, factors associated with longer freedom from any PA reintervention included lower postrepair RV:aortic pressure ratio and larger original conduit size.We were able to obtain follow-up data for the majority of patients, which demonstrated freedom from PA reintervention for two thirds of patients. The time course of and risk factors for conduit reintervention in this cohort appeared similar to previously reported findings in patients who received RV-PA conduits in early childhood for other anomalies. Relative to the severity of baseline pulmonary vascular anatomy in TOF with MAPCAs, reinterventions on the reconstructed PAs were uncommon after repair according to our approach, and major reinterventions were rare. Nevertheless, PA reinterventions are an important aspect of the overall management strategy.
View details for PubMedID 29352588
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Anesthetic Management During Surgery for Tetralogy of Fallot With Pulmonary Atresia and Major Aortopulmonary Collateral Arteries
WORLD JOURNAL FOR PEDIATRIC AND CONGENITAL HEART SURGERY
2018; 9 (2): 236–41
Abstract
Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals (TOF/PA/MAPCAs) is a heterogeneous disease with varying degrees of severity, requiring complex anesthetic management. Our institution has adopted the approach of early complete repair with incorporation of all lung segments, extensive lobar and branch segmental pulmonary artery reconstruction, and ventricular septal defect closure. While the surgical management of TOF/PA/MAPCAs has been extensively described and varies depending on the institution, there is a paucity of literature on the anesthetic management for such procedures. Herein, we describe our anesthetic management based on our own institution's surgical approach at Lucile Packard Children's Hospital/Stanford University.
View details for PubMedID 29544416
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Selected 2016 Highlights in Congenital Cardiac Anesthesia
JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
2017; 31 (6): 1927–33
View details for PubMedID 29074129
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Bronchoscopy in children with tetralogy of fallot, pulmonary atresia, and major aortopulmonary collaterals.
Pediatric pulmonology
2017
Abstract
Children with Tetralogy of Fallot, Pulmonary Atresia, and Major Aortopulmonary Collaterals (TOF/PA/MAPCAs) undergoing unifocalization surgery are at risk for developing more postoperative respiratory complications than children undergoing other types of congenital heart surgery. Bronchoscopy is used in the perioperative period for diagnostic and therapeutic purposes. In this study, we describe bronchoscopic findings and identify factors associated with selection for bronchoscopy.Retrospective case-control.All patients with TOF/PA/MAPCAs who underwent unifocalization surgery from September 2005 through March 2016 were included. Patients who underwent bronchoscopy in the perioperative period were compared to a randomly selected cohort of 172 control patients who underwent unifocalization without bronchoscopy during the study period.Forty-three children underwent perioperative bronchoscopy at a median of 9 days postoperatively. Baseline demographics were similar in bronchoscopy patients and controls. Patients who underwent bronchoscopy were more likely to have a chromosome 22q11 deletion and were more likely have undergone unifocalization surgery without intracardiac repair. These patients had a longer duration of mechanical ventilation, ICU duration, and length of hospitalization. Abnormalities were detected on bronchoscopy in 35 patients (81%), and 20 (35%) of bronchoscopy patients underwent a postoperative intervention related to abnormalities identified on bronchoscopy.Bronchoscopy is a useful therapeutic and diagnostic instrument for children undergoing unifocalization surgery, capable of identifying abnormalities leading to an additional intervention in over one third of patients. Special attention should be given to children with a 22q11 deletion to expedite diagnosis and intervention for possible airway complications.
View details for DOI 10.1002/ppul.23732
View details for PubMedID 28504356
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Programmatic Approach to Management of Tetralogy of Fallot With Major Aortopulmonary Collateral Arteries A 15-Year Experience With 458 Patients
CIRCULATION-CARDIOVASCULAR INTERVENTIONS
2017; 10 (4)
Abstract
Tetralogy of Fallot with major aortopulmonary collateral arteries is a complex and heterogeneous condition. Our institutional approach to this lesion emphasizes early complete repair with the incorporation of all lung segments and extensive lobar and segmental pulmonary artery reconstruction.We reviewed all patients who underwent surgical intervention for tetralogy of Fallot and major aortopulmonary collateral arteries at Lucile Packard Children's Hospital Stanford (LPCHS) since November 2001. A total of 458 patients underwent surgery, 291 (64%) of whom underwent their initial procedure at LPCHS. Patients were followed for a median of 2.7 years (mean 4.3 years) after the first LPCHS surgery, with an estimated survival of 85% at 5 years after first surgical intervention. Factors associated with worse survival included first LPCHS surgery type other than complete repair and Alagille syndrome. Of the overall cohort, 402 patients achieved complete unifocalization and repair, either as a single-stage procedure (n=186), after initial palliation at our center (n=74), or after surgery elsewhere followed by repair/revision at LPCHS (n=142). The median right ventricle:aortic pressure ratio after repair was 0.35. Estimated survival after repair was 92.5% at 10 years and was shorter in patients with chromosomal anomalies, older age, a greater number of collaterals unifocalized, and higher postrepair right ventricle pressure.Using an approach that emphasizes early complete unifocalization and repair with incorporation of all pulmonary vascular supply, we have achieved excellent results in patients with both native and previously operated tetralogy of Fallot and major aortopulmonary collateral arteries.
View details for DOI 10.1161/CIRCINTERVENTIONS.116.004952
View details for PubMedID 28356265
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Acute Kidney Injury in Patients Undergoing the Extracardiac Fontan Operation With and Without the Use of Cardiopulmonary Bypass
PEDIATRIC CRITICAL CARE MEDICINE
2017; 18 (1): 34-43
Abstract
To describe the prevalence and risk factors for acute kidney injury in patients undergoing the extracardiac Fontan operation with and without cardiopulmonary bypass, and to determine whether acute kidney injury is associated with duration of mechanical ventilation, cardiovascular ICU and hospital postoperative length of stay, and early mortality.Single-center retrospective cohort study.Pediatric cardiovascular ICU, university-affiliated children's hospital.Patients with a preoperative creatinine before undergoing first-time extracardiac Fontan between January 1, 2004, and April 30, 2012.None.Acute kidney injury occurred in 55 of 138 patients (39.9%), including 41 (29.7%) with stage 1, six (4.4%) with stage 2, and eight (5.8%) with stage 3 acute kidney injury. Cardiopulmonary bypass was strongly associated with a higher risk of any acute kidney injury (adjusted odds ratio, 4.8 [95% CI, 1.4-16.0]; p = 0.01) but not stage 2/3 acute kidney injury. Lower renal perfusion pressure on the day of surgery (postoperative day, 0) was associated with a higher risk of stage 2/3 acute kidney injury (adjusted odds ratio, 1.2 [95% CI, 1.0-1.5]; p = 0.03). Higher vasoactive-inotropic score on postoperative day 0 was associated with a higher risk for stage 2/3 acute kidney injury (adjusted odds ratio, 1.9 [95% CI, 1.0-3.4]; p = 0.04). Stage 2/3 acute kidney injury was associated with longer cardiovascular ICU length of stay (mean, 7.3 greater d [95% CI, 3.4-11.3]; p < 0.001) and hospital postoperative length of stay (mean, 6.4 greater d [95% CI, 0.06-12.5]; p = 0.04).Postoperative acute kidney injury in patients undergoing the extracardiac Fontan operation is common and is associated with lower postoperative renal perfusion pressure and higher vasoactive-inotropic score. Cardiopulmonary bypass was strongly associated with any acute kidney injury, although not stage 2/3 acute kidney injury. Stage 2/3 acute kidney injury is a compelling risk factor for longer cardiovascular ICU and hospital postoperative length of stay. Increased attention to and management of renal perfusion pressure may reduce postoperative acute kidney injury and improve outcomes.
View details for DOI 10.1097/PCC.0000000000000984
View details for Web of Science ID 000392249300005
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Cognitive Dysfunction in Children with Heart Disease: The Role of Anesthesia and Sedation.
Congenital heart disease
2016; 11 (3): 221-229
Abstract
As physicians and caregivers of children with congenital heart disease, we are aware of the increasing need for procedures requiring anesthesia. While these procedures may be ideal for medical and cardiac surgical management, the risks and benefits must be assessed carefully. There are well known risks of cardiovascular and respiratory complications from anesthesia and sedation and a potentially under-appreciated risk of neurocognitive dysfunction. Both animal and human studies support the detrimental effects of repeated anesthetic exposure on the developing brain. Although the studies in humans are less convincing of this risk, the Society of Pediatric Anesthesia jointly with SmartTots provided a consensus statement on the use of anesthetic and sedative drugs in infants and toddlers when speaking to families. (www.pedsanesthesia.org; http://smarttots.org/wp-content/uploads/2015/10/ConsensusStatementV910.5.2015.pdf). An excerpt of the statement is "Concerns regarding the unknown risk of anesthetic exposure to your child's brain development must be weighed against the potential harm associated with cancelling or delaying a needed procedure. Each child's care must be evaluated individually based on age, type, and urgency of the procedure and other health factors. This review provides a summary of the current evidence regarding anesthesia-induced neurotoxicity and the developing brain and its implications for children with congenital heart disease.
View details for DOI 10.1111/chd.12352
View details for PubMedID 27228360
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Anesthetic and Sedative Neurotoxicity in the Patient with Congenital Heart Disease
ANESTHESIA FOR CONGENITAL HEART DISEASE, 3RD EDITION
2015: 184–98
View details for Web of Science ID 000385225800010
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Management of high-risk reentry sternotomy in an infant for repair of a giant pseudoaneurysm of the right ventricular outflow tract.
Annals of cardiac anaesthesia
2014; 17 (1): 59-61
Abstract
Improved survival from congenital heart disease has led to an increasing need for complex reoperation by reentrant sternotomy. Peripheral cannulation and initiation of cardiopulmonary bypass prior to sternotomy to avoid the risk of cardiac injury and massive hemorrhage is an option in adults and larger children, but femoral vessel size precludes this strategy in infants. We describe the management of a high-risk reentry sternotomy in an infant for repair of a giant pseudoaneurysm after prior homograft repair of tetralogy of Fallot, using surgical dissection for suprasternal cannulation of the innominate artery and subxyphoid cannulation of the inferior vena cava.
View details for DOI 10.4103/0971-9784.124145
View details for PubMedID 24401306
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Anesthesia and the developing brain: relevance to the pediatric cardiac surgery.
Brain sciences
2014; 4 (2): 295-310
Abstract
Anesthetic neurotoxicity has been a hot topic in anesthesia for the past decade. It is of special interest to pediatric anesthesiologists. A subgroup of children potentially at greater risk for anesthetic neurotoxicity, based on a prolonged anesthetic exposure early in development, are those children receiving anesthesia for surgical repair of congenital heart disease. These children have a known risk of neurologic deficit after cardiopulmonary bypass for surgical repair of congenital heart disease. Yet, the type of anesthesia used has not been considered as a potential etiology for their neurologic deficits. These children not only receive prolonged anesthetic exposure during surgical repair, but also receive repeated anesthetic exposures during a critical period of brain development. Their propensity to abnormal brain development, as a result of congenital heart disease, may modify their risk of anesthetic neurotoxicity. This review article provides an overview of anesthetic neurotoxicity from the perspective of a pediatric cardiac anesthesiologist and provides insight into basic science and clinical investigations as it relates to this unique group of children who have been studied over several decades for their risk of neurologic injury.
View details for DOI 10.3390/brainsci4020295
View details for PubMedID 24961762
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Acute and sustained isoflurane neuroprotection: The effect of culture age and duration of oxygen and glucose deprivation
BRAIN INJURY
2013; 27 (4): 444-453
Abstract
Organotypic hippocampal slice (OHS) cultures provide the opportunity to dissect factors influencing volatile anaesthetic neuroprotective efficacy. It was hypothesized that three conditions-OHS culture age, oxygen glucose deprivation (OGD) duration and day of evaluation for cell death after OGD-influence isoflurane's ability to provide acute and sustained protection against OGD-induced cell death.OHS were prepared from PND 9-11 rat pups and maintained in vitro for 0.5, 1, 2 or 3 weeks. The slices were exposed to OGD for 0, 10, 30, 60 or 90 minutes with or without 1.5% isoflurane. Sytox staining was used to determine the amount of cell death on post-OGD days 1, 3 and 7 and was compared to the amount of cell death in culture-age matched controls (no OGD).The duration of OGD necessary to produce cell death was inversely related to culture age. All culture ages showed evidence of both acute and sustained neuroprotection, but the magnitude of protection depended on OHS culture age, duration of OGD and post-OGD day of evaluation. In 1 and 2-week old slices early isoflurane neuroprotection was best observed with 90 minutes OGD and late isoflurane protection was best observed with 10 minutes OGD.In OHS, acute and sustained isoflurane neuroprotection in OGD-induced cell death is dependent on the conditions being studied.
View details for DOI 10.3109/02699052.2012.750755
View details for Web of Science ID 000316954300009
View details for PubMedID 23473549
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Anesthesia during surgical repair for congenital heart disease and the developing brain: neurotoxic or neuroprotective?
PEDIATRIC ANESTHESIA
2011; 21 (5): 554-559
View details for DOI 10.1111/j.1460-9592.2011.03586.x
View details for Web of Science ID 000289469500010
View details for PubMedID 21481079
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The effect of sevoflurane on neuronal degeneration and GABAA subunit composition in a developing rat model of organotypic hippocampal slice cultures.
Journal of neurosurgical anesthesiology
2010; 22 (3): 220-9
Abstract
The GABA(A) receptor subunit composition undergoes a switch from a predominantly alpha2 to a predominantly alpha1 around postnatal day (PND) 7 in a rat pup. This developmental switch in the GABA(A) receptor subunit composition changes the kinetics and pharmacologic properties of the GABA(A) receptor. Using a developmental organotypic hippocampal slice model, we hypothesized that the developmental changes in the GABA(A) receptor subunit composition may promote neurodegeneration after exposure to sevoflurane.Organotypic hippocampal slices (OHS) were prepared from rat pups on PND 4, 7, and 14 and exposed to 2.0% sevoflurane or air for 5 hours. Hippocampal CA1, CA3, and dentate gyrus neuronal survival and GABA(A) receptor subunit composition were assessed immediately, 24 and 72 hours after exposure and compared with air.Early cell death immediately after exposure to sevoflurane was statistically significant in the PND14 (P<0.001). At 24 hours, cell death was not significant for any PND age-examined OHS. However, at 72 hours, cell death was significant in the OHS prepared from the PND7 and 4 rat pups (P<0.001). In further analysis, either a decrease in the alpha1 and/or increase in the alpha2 subunit composition promoted cell survival in the PND 4 and 7 OHS. On PND14, cell survival was promoted by an increase in the alpha1 subunit composition.This in vitro investigation supports an age-dependent and GABA(A) receptor subunit composition relationship between 2.0% sevoflurane exposure and cell death.
View details for DOI 10.1097/ANA.0b013e3181e16c89
View details for PubMedID 20548169
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Society for Pediatric Anesthesia/American Academy of Pediatrics/Congenital Cardiac Anesthesia Society: winter meeting review.
Anesthesia and analgesia
2010; 110 (1): 266-71
View details for DOI 10.1213/01.ane.0000365944.51101.61
View details for PubMedID 20023193
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Oxygen and glucose deprivation in an organotypic hippocampal slice model of the developing rat brain: the effects on N-methyl-D-aspartate subunit composition.
Anesthesia and analgesia
2009; 109 (1): 205-10
Abstract
Organotypic hippocampal slices (OHS) are commonly used to screen for neuroprotective effects of pharmacological agents relevant to pediatric brain injury. The importance of donor rat pup age and N-methyl-D-aspartate (NMDA) receptor subunit composition have not been addressed. In this study, we evaluated the age-dependent effect of oxygen-glucose deprivation (OGD) in the developing rat brain and determined whether OGD modulates the NMDA receptor subunit composition.OHS were prepared from rat pups on postnatal days (PND) 4, 7, 14, and 21 and cultured 7 days in vitro. The slices were exposed to OGD for durations of 5-60 min. After 24 and 72 h, OHS survival and NMDA subunit composition were assessed.Cell death was evident in OHS prepared from PND 14 and 21 rat pups (P < 0.001) with OGD durations of 5 and 10 min, respectively. In OHS prepared from PND7 rat pups, neurodegeneration was not evident until 20 min OGD (P < 0.001). Exposure to OGD in OHS prepared from PND4 and PND7 rat pups was associated with a transition in the NMDA receptor subunit composition from NR2B predominant to NR2A predominant subunit composition.This in vitro neonatal rat pup investigation using OHS supports both an age and an NMDA receptor subunit composition-dependent relationship between OGD and neuronal cell death.
View details for DOI 10.1213/ane.0b013e3181a27e37
View details for PubMedID 19535712
View details for PubMedCentralID PMC4175416
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Effect of lipophilicity of Mn (III) ortho N-alkylpyridyl- and diortho N, N'-diethylimidazolylporphyrins in two in-vitro models of oxygen and glucose deprivation-induced neuronal death.
Free radical research
2009; 43 (4): 329-39
Abstract
In vivo investigations have confirmed the beneficial effects of hydrophilic, cationic Mn(III) porphyrin-based catalytic antioxidants in different models of oxidative stress. Using a cell culture model of rat mixed neuronal/glial cells, this study investigated the effect of MnTnOct-2-PyP5+ on oxygen and glucose deprivation (OGD)-induced cell death as compared to the effects of widely studied hydrophilic analogues MnTE-2-PyP5+ and MnTDE-2-ImP5+ and a standard compound, dizocilpine (MK-801). It was hypothesized that the octylpyridylporphyrin, MnTnOct-2-PyP5+, a lipophilic but equally potent antioxidant as the other two porphyrins, would be more efficacious in reducing OGD-induced cell death due to its higher bioavailability. Cell death was evaluated at 24 h using lactate dehydrogenase (LDH) release and propidium iodide staining. At concentrations from 3-100 microM, all three porphyrins reduced cell death as compared to cultures exposed to OGD alone, the effects depending upon the concentrations and type of treatment. To assess the effect of lipophilicity the additional experiments were performed using submicromolar concentrations of MnTnOct-2-PyP5+ in an organotypic hippocampal slice model of OGD with propidium iodide and Sytox staining. When compared to oxygen and glucose deprivation alone, concentrations of MnTnOct-2-PyP5+ as low as 0.01 microM significantly (p<0.001; power 1.0) reduced neuronal cells similar to control. This is the first in vitro study on the mammalian cells which indicates that MnTnOct-2-PyP5+ is up to 3000-fold more efficacious than equally potent hydrophilic analogues, due entirely to its increased bioavailability. Such remarkable increase in efficacy parallels 5.7-orders of magnitude increase in lipophilicity of MnTnOct-2-PyP5+ (log P=-0.77) when compared to MnTE-2-PyP5+ (log POW=-6.43), POW being partition coefficient between n-octanol and water.
View details for DOI 10.1080/10715760902736283
View details for PubMedID 19259881
View details for PubMedCentralID PMC3160267
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NMDA-induced apoptosis in mixed neuronal/glial cortical cell cultures: the effects of isoflurane and dizocilpine.
Journal of neurosurgical anesthesiology
2006; 18 (4): 240-6
Abstract
In animal models of severe ischemia, it has not been uniformly observed that anesthetics are protective. However, anesthetics have not been evaluated in the presence of a mild excitotoxic insult. We hypothesized that in the presence of a mild excitotoxic insult, 3 microm N-methyl-D-aspartate (NMDA), isoflurane may prevent apoptotic cell death. Primary mixed neuronal/glial cultures were prepared from fetal rat brains. Mature cultures were exposed to dissolved isoflurane [0 mM, 0.4 mM (1.8 minimum alveolar concentration) or 1.6 mM (7 minimum alveolar concentration)] or dizocilpine (10 microM), and NMDA (0 or 3 microM) at 37 degrees C for 30 minutes. Apoptosis was assessed using terminal-deoxy-nucleotidyl end-nick labeling oligonucleosomal DNA fragmentation enzyme-linked immunosorbent assay, and caspases-3 and -9 activation assays. NMDA (3 muM) induced apoptosis in mixed neuronal/glial cell cultures. Apoptosis induced by 3 microm NMDA was caspase-3 but not caspase-9 mediated. In the presence of a mild excitotoxic insult, this investigation showed an attenuation of apoptotic cell death by dizocilpine, but not isoflurane.
View details for PubMedID 17006121
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Isoflurane-induced neuronal degeneration: an evaluation in organotypic hippocampal slice cultures.
Anesthesia and analgesia
2005; 101 (3): 651-7, table of contents
Abstract
Prolonged exposure of postnatal day (PND) 7 rat pups to anesthetics, which act via N-methyl-D-aspartate antagonism and/or gamma-amino butyric acid enhancement, causes neurodegeneration and persistent behavioral deficits. We studied these findings in vitro and determined whether the age of rat pups used for study or duration of anesthetic exposure modulates resultant neurodegeneration. Organotypic hippocampal slices (OHSs) were prepared from rat pups on PNDs 4, 7, and 14 and cultured 7 or 14 days in vitro. The slices were exposed to 1.5% isoflurane or fresh gas for durations of 1, 3, or 5 h. Hippocampal CA1, CA3, and dentate gyrus neuronal survival was assessed 3 days later. Neuronal cell death was greatest in OHSs prepared from PND 7 rat pups (P < 0.001) and was most evident after 5 h exposure to isoflurane (P < 0.001). By eliminating variables such as hemodynamics, nutrition, oxygenation, and carbon dioxide elimination, this in vitro investigation supports both an age- and duration-dependent relationship between 1.5% isoflurane exposure and perinatal neuronal death.
View details for DOI 10.1213/01.ane.0000167382.79889.7c
View details for PubMedID 16115969
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Utility of airway exchange catheters in pediatric patients with a known difficult airway.
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
2005; 6 (4): 454-6
Abstract
To evaluate the utility of the Cook airway exchange catheter (CAEC) for extubation/reintubation in pediatric patients with a known difficult airway.Prospective, nonrandomized.Pediatric intensive care unit; single academic institution.Twenty intubated children =18 yrs of age with a known difficult airway requiring extubation.The CAEC was inserted into the trachea before extubation in children with a known difficult airway who were at risk for a difficult reintubation. The CAEC provided a means of a "guided" reintubation while maintaining the ability to provide supplemental oxygenation directly into the trachea.The respiratory rate, oxygen saturation, and amount of oxygen administered were measured immediately before extubation and at 5-, 15-, 30-, and 60-min intervals thereafter. In addition, the child's ability to tolerate the CAEC was noted and rated (0 = tolerable without difficulty, 1 = tolerable with difficulty, 2 = intolerable). No sedatives were administered in the presence of the CAEC. The duration of the CAEC placement was dependent on the satisfaction of the child's airway patency as determined by the unlikely need for reintubation. Five of the 20 (25%) children who had been extubated were reintubated in the intensive care unit with the assistance of the CAEC. Three of the five (60%) children were reintubated for upper airway obstruction. The ability to provide supplemental oxygen through the CAEC into the trachea during reintubation diminished the potential for hypoxia and maintained the ability to reintubate the trachea using the CAEC as a guidewire to pass an endotracheal tube.In children with a known difficult airway who are at risk for a difficult reintubation, the CAEC is a useful tool for a trial of extubation in the intensive care unit.
View details for DOI 10.1097/01.PCC.0000163739.82584.C6
View details for PubMedID 15982434
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Apoptosis is not enhanced in primary mixed neuronal/glial cultures protected by isoflurane against N-methyl-D-aspartate excitotoxicity.
Anesthesia and analgesia
2004; 99 (6): 1708-14, table of contents
Abstract
Volatile anesthetics reduce acute excitotoxic cell death in primary neuronal/glial cultures. We hypothesized that cells protected by isoflurane against N-methyl-d-aspartate (NMDA)-induced necrosis would instead become apoptotic. Primary mixed neuronal/glial cultures prepared from fetal rat brain were exposed to dissolved isoflurane (0 mM, 0.4 mM [1.8 minimum alveolar anesthetic concentration], or 1.6 mM [7 minimum alveolar anesthetic concentration]) and NMDA (0 or 100 microM) at 37 degrees C for 30 min. Dizocilpine (10 microM) plus 100 microM NMDA served as a positive control. Necrosis and apoptosis were assessed at 24 and/or 48 h after exposure by using Hoechst/propidium iodide staining, terminal-deoxynucleotidyl transferase end-nick labeling, DNA fragmentation enzyme-linked immunoabsorbence, and caspase-3 activity assays. NMDA increased the number of necrotic cells. Isoflurane (1.6 mM) and dizocilpine partially reduced cellular necrosis but did not increase the number of morphologically apoptotic or apoptotic-like cells resulting from exposure to 100 microM NMDA at 24 h. At 48 h, no evidence was found to indicate that cells protected by isoflurane had become apoptotic or apoptotic-like. However, cells protected by dizocilpine against necrosis showed evidence of caspase-3-mediated apoptosis. These in vitro data do not support the hypothesis that isoflurane protection against acute excitotoxic necrosis results in apoptosis.
View details for DOI 10.1213/01.ANE.0000136474.35627.FF
View details for PubMedID 15562059
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Perioperative management of diabetes insipidus in children.
Journal of neurosurgical anesthesiology
2004; 16 (3): 220-5
Abstract
Managing children with diabetes insipidus (DI) in the perioperative period is complicated and frequently associated with electrolyte imbalance compounded by over- or underhydration. In this study the authors developed and prospectively evaluated a multidisciplinary approach to the perioperative management of DI with a comparison to 19 historical control children. Eighteen children either with preoperative DI or undergoing neurosurgical operations associated with a high risk for developing postoperative DI were identified and managed using a standardized protocol. In all patients in whom DI occurred during or after surgery, a continuous intravenous infusion of aqueous vasopressin was initiated and titrated until antidiuresis was established. Intravenous fluids were given as normal saline and restricted to two thirds of the estimated maintenance rate plus amounts necessary to replace blood losses and maintain hemodynamic stability. In all children managed in this fashion, perioperative serum sodium concentrations were generally maintained between 130 and 150 mEq/L, and no adverse consequences of this therapy developed. In the 24-hour period evaluated, the mean change in serum sodium concentrations between the historical controls was 17.6 +/- 9.2 mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol. Hyponatremia occurred less frequently in the children managed with this protocol compared with historical controls.
View details for PubMedID 15211159
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Perioperative management of diabetes insipidus in children [corrected].
Journal of neurosurgical anesthesiology
2004; 16 (1): 14-9
Abstract
Managing children with diabetes insipidus (DI) in the perioperative period is complicated and frequently associated with electrolyte imbalance compounded by over- or underhydration. In this study the authors developed and prospectively evaluated a multidisciplinary approach to the perioperative management of DI with a comparison to 19 historical control children. Eighteen children either with preoperative DI or undergoing neurosurgical operations associated with a high risk for developing postoperative DI were identified and managed using a standardized protocol. In all patients in whom DI occurred during or after surgery, a continuous intravenous infusion of aqueous vasopressin was initiated and titrated until antidiuresis was established. Intravenous fluids were given as normal saline and restricted to two thirds of the estimated maintenance rate plus amounts necessary to replace blood losses and maintain hemodynamic stability. In all children managed in this fashion, perioperative serum sodium concentrations were generally maintained between 130 and 150 mEq/L, and no adverse consequences of this therapy developed. In the 24-hour period evaluated, the mean change in serum sodium concentrations between the historical controls was 17.6 +/- 9.2 mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol. Hyponatremia occurred less frequently in the children managed with this protocol compared with historical controls.
View details for PubMedID 14676564
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Desflurane and sevoflurane attenuate oxygen and glucose deprivation-induced neuronal cell death.
Journal of neurosurgical anesthesiology
2003; 15 (3): 193-9
Abstract
Neuronal cell death may occur via two pathways: those causing necrosis or those causing apoptosis. Apoptosis can be activated during periods of stress such as oxygen and glucose deprivation. Anesthetic agents such as desflurane or sevoflurane can attenuate early neuronal necrotic death, but their effect on oxygen and glucose deprivation-induced apoptosis has not been investigated. Neuronal cell cultures were prepared from neonatal rat cortex and were used between 10 and 14 days in vitro. The neuronal cell cultures were pretreated 30 minutes prior to oxygen and glucose deprivation with either desflurane or sevoflurane (N = 18). Three concentrations of each anesthetic were evaluated. The cultures were then deprived of oxygen and glucose for 30, 60, or 90 minutes. Treatment with desflurane or sevoflurane was continued during the period of oxygen and glucose deprivation. Forty-eight hours after exposure, the cells were examined for apoptosis using TUNEL and DNA gel electrophoresis. Comparisons were made to neuronal cortical cell cultures exposed to oxygen and glucose deprivation alone (N = 9). This in vitro model of oxygen and glucose deprivation was successful in producing neuronal cell death during the exposure times examined. During 30-, 60-, and 90-minute periods of oxygen and glucose deprivation, both desflurane and sevoflurane significantly ( approximately 98%) attenuated neuronal cell death regardless of concentration.
View details for PubMedID 12826966
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Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by halothane and isoflurane.
Anesthesia and analgesia
2001; 93 (5): 1281-7
Abstract
Both in vitro and in vivo evidence supports the reduction of early ischemic, both global and focal, brain injury by volatile anesthetics. However, the protection afforded by volatile anesthetics in later neuronal death, i.e., apoptosis, caused by global ischemia has not been investigated. We induced oxygen and glucose deprivation in neuronal cortical cell cultures prepared from newborn rats on in vitro Days 10-14. This hypoxic (PO2 <50 mm Hg) condition was maintained continuously (30, 60, and 90 min). In a separate experiment, the neuronal cell cultures were exposed to isoflurane (1.13%, 2.3%, or 3.3%) or halothane (1.7%, 3.4%, or 5.1%) before oxygen and glucose deprivation, with continued exposure to isoflurane or halothane during oxygen and glucose deprivation. After 48 h, neuronal apoptosis was assessed with terminal deoxynucleotidyl transferase-mediated in situ nick-end labeling and DNA gel electrophoresis. Oxygen and glucose deprivation (30, 60, and 90 min) caused significant apoptosis of cerebral cortical cultured neurons. However, pretreatment and continued treatment during the period of oxygen and glucose deprivation with halothane or isoflurane resulted in a concentration-dependent attenuation of oxygen and glucose deprivation-induced neuronal apoptosis.This is the first investigation to evaluate the effect of volatile anesthetics on oxygen and glucose deprivation-induced neuronal apoptosis. Oxygen and glucose deprivation-induced neuronal apoptosis can be decreased by prior and continued administration of halothane or isoflurane.
View details for PubMedID 11682415
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Intraoperative cardiac arrest in a neurosurgical patient: what are the options?
Journal of neurosurgical anesthesiology
2000; 12 (1): 57-9
Abstract
Intraoperative cardiac arrest is uncommon. We describe a case of intraoperative cardiac arrest in a patient undergoing anesthesia for surgical repair of an intracranial arteriovenous malformation (AVM).
View details for PubMedID 10636623
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Incidence of venous air embolism during craniectomy for craniosynostosis repair.
Anesthesiology
2000; 92 (1): 20-3
Abstract
Investigations to determine the incidence of venous air embolism in children undergoing craniectomy for craniosynostosis repair have been limited, although venous air embolism has been suspected as the cause of hemodynamic instability and sometimes death. A precordial Doppler ultrasonic probe is an accepted method for detection of venous air embolism and is readily available at most institutions.A prospective study was conducted using a precordial Doppler ultrasonic probe in children undergoing craniectomy for craniosynostosis repair. The Doppler signal was continuously monitored intraoperatively for characteristic changes of venous air embolism. A recording was made of the precordial Doppler probe pulses, which was later reviewed by a neuroanesthesiologist, blinded to the intraoperative events. This information was correlated with the intraoperative events and episodes of venous air embolism were graded.Twenty-three patients were enrolled in the study during the 2-yr study period. Nineteen patients (82.6%) demonstrated 64 episodes of venous air embolism; six patients (31.6%) had hypotension associated with venous air embolism. Thirty-two episodes of hypotension were demonstrated in eight patients (34.7%). None of the patients developed cardiovascular collapse.The incidence of venous air embolism in our study of 23 children undergoing craniectomy for craniosynostosis was 82.6%. Though most episodes of venous air embolism during craniosynostosis repair are without hemodynamic consequences, the preemptive placement of a precordial Doppler ultrasonic probe is a noninvasive, economic, and safe method for the detection of venous air embolism. Prompt recognition may allow for the early initiation of therapy, thereby decreasing morbidity and mortality rates related to venous air embolism.
View details for PubMedID 10638894
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Somatosensory-evoked potentials during aortic coarctation repair.
Journal of cardiothoracic and vascular anesthesia
1999; 13 (5): 538-43
Abstract
To determine the incidence of somatosensory-evoked potential (SSEP) changes and the interventions based on these changes during aortic coarctation repair.Retrospective review.Single-institution, university hospital.Eighty-four children who had undergone surgical repair of aortic coarctation from January 1984 to May 1996.SSEPs were monitored in all patients throughout the procedure. A persistent decrease in amplitude greater than 50% from baseline was considered significant. Duration of SSEP changes in relation to the time course of surgical repair and whether a surgical or anesthetic intervention resulted from a change in SSEPs were documented.Eighty-four patients underwent 87 surgical procedures. SSEP changes occurred in 40% of the procedures: 38.5% with repair and 15% with test clamp, with 9% occurring during both test clamp and repair. Interventions, which included repositioning the aortic cross-clamp, elevating blood pressure, and aborting surgery, occurred in 26.4% of all procedures based on SSEP changes. No patient sustained a neurologic deficit.This is the largest series to date describing the use of SSEPs in aortic coarctation repair. These SSEP changes were often immediately amenable to changes in surgical and anesthetic management. SSEP changes and interventions based on these changes occurred with a considerable frequency.
View details for PubMedID 10527221
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The imposed work of breathing is less with the laryngeal mask airway compared with endotracheal tubes.
Anesthesia and analgesia
1999; 89 (3): 644-6
View details for PubMedID 10475296
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Blood loss and transfusion practice in the perioperative management of craniosynostosis repair.
Journal of neurosurgical anesthesiology
1999; 11 (3): 167-72
Abstract
During the past 5 years, the surgical repair for sagittal synostosis has been modified to a more complex and involved procedure. This led to a retrospective evaluation of the current transfusion practice in a large series of craniosynostosis repairs. The charts of 76 patients (81 surgical procedures) undergoing craniosynostosis repair from January 1990 to November 1996 were examined. The calculated volume of blood loss (BL) was determined for each surgical procedure and related to the estimated blood volume (EBV) and acceptable blood loss (ABL). The anesthesiologist's ability to estimate BL was compared with the calculated blood loss (CBL). In most surgical procedures for craniosynostosis, especially in the complex sagittal repairs, CBL was underestimated and exceeded ABL. Packed red blood cell transfusion occurred in 96.3% of the patients and was appropriate for most procedures based on ABL. Thus, transfusion for craniosynostosis repair is almost inevitable, and the preventive preparation of blood on the order of the mean estimated blood loss (EBL) plus 2 SD is appropriate. With the increased complexity of sagittal repair and its performance in a younger population, the cosmetic benefit of surgical repair has major implications for management of blood and fluids.
View details for PubMedID 10414670
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A randomized trial of the effect of midazolam on intraocular pressure.
Journal of glaucoma
1999; 8 (3): 204-7
Abstract
The effect of midazolam on intraocular pressure (IOP) in adults was studied as an initial step in determining whether it can be used as a preoperative anxiolytic or sedative agent in children with glaucoma who are undergoing examination for IOP measurements.This study followed a prospective, placebo controlled, randomized, double masked design. Fifty-five participants were enrolled after informed consent was obtained. Each enrolled patient underwent a brief history and eye examination. Measurements of IOP were taken at baseline and 5, 10, and 15 minutes after intravenous administration of 1 mg midazolam or placebo. IOP was the primary outcome measured.There was no difference in IOP fluctuation from baseline between patients who received midazolam and those who received placebo.Early results indicate that because midazolam does not lower IOP, it may be a useful adjunct to ketamine anesthesia in children with glaucoma undergoing ophthalmologic examination under anesthesia. However, studies of midazolam must be conducted in children and patients with glaucoma before its use in these populations can be recommended.
View details for PubMedID 10376262
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Spinal anesthesia for nonpulmonary surgery in a lung transplant recipient.
Journal of neurosurgical anesthesiology
1999; 11 (1): 46-8
Abstract
The anesthetic implications for patients requiring anesthesia for surgery after lung transplantation have not been thoroughly studied. The use of spinal anesthesia in patients undergoing lumbar laminectomy has been well described. This case demonstrates the use of spinal anesthesia for lumbar laminectomy in a patient who had previously undergone a bilateral lung transplantation. Spinal anesthesia was used to minimize the risk of respiratory complications such as aspiration, atelectasis, and pneumonia that may be associated with administration of a general anesthetic.
View details for PubMedID 9890386