Colleen Gruenwald

Risk, Clinical Features, and Outcomes of Thrombosis Associated With Pediatric Cardiac Surgery

Background— Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. Methods and Results— We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/109 cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. Conclusions— Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.

Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: A randomized controlled trial

Objective This study compared the effects of reconstituted fresh whole blood against standard blood component therapy in neonates undergoing cardiac surgery. Methods Patients less than 1 month of age were randomized to receive either reconstituted fresh whole blood (n = 31) or standard blood component therapy (n = 33) to prime the bypass circuit and for transfusion during the 24 hours after cardiopulmonary bypass. Primary outcome was chest tube drainage; secondary outcomes included transfusion needs, inotrope score, ventilation time, and hospital length of stay. Results Patients who received reconstituted fresh whole blood had significantly less postoperative chest tube volume loss per kilogram of body weight (7.7 mL/kg vs 11.8 mL/kg; P = .03). Standard blood component therapy was associated with higher inotropic score (6.6 vs 3.3; P = .002), longer ventilation times (164 hours vs 119 hours; P = .04), as well as longer hospital stays (18 days vs 12 days; P = .006) than patients receiving reconstituted fresh whole blood. Of the different factors associated with the use of reconstituted fresh whole blood, lower platelet counts at 10 minutes and at the end of cardiopulmonary bypass, older age of cells used in the prime and throughout bypass, and exposures to higher number of allogeneic donors were found to be independent predictors of poor clinical outcomes. Conclusions Reconstituted fresh whole blood used for the prime, throughout cardiopulmonary bypass, and for all transfusion requirements within the first 24 hours postoperatively results in reduced chest tube volume loss and improved clinical outcomes in neonatal patients undergoing cardiac surgery.

Improved Outcomes Associated With Intraoperative Steroid Use in High-Risk Pediatric Cardiac Surgery

BACKGROUND Corticosteroids are commonly administered perioperatively in pediatric cardiac surgery to reduce cardiopulmonary bypass induced inflammation. However, their effects on outcomes and potential for adverse events are not well defined. METHODS A review was undertaken of cardiac operations between September 2004 and December 2007 carrying a comprehensive Aristotle score 10 or greater. A nonrandomized comparison was undertaken comparing those patients having received intraoperative methylprednisolone at anesthesia induction or in the bypass circuit prime with those who did not. To account for nonrandom assignment of steroid use, a propensity model was created to establish each patients probability of having received steroids (∼150 variables evaluated, 17 in final model, c-stat 0.94, p < 0.001). Associations between postoperative outcomes and intraoperative steroid use were modeled in multivariable linear regression models adjusted for propensity score and relevant surgical characteristics. RESULTS In 221 identified cases, 134 (61%) patients received intraoperative steroids; of these, 44 (33%) also received preoperative doses. In propensity-adjusted regression models, intraoperative steroid use was associated with lower chest tube volume loss in the first 24 postoperative hours (-5.3 mL/kg, p < 0.001), and shorter durations of stay in intensive care (-2.3 days, p < 0.001) and hospital (-4.1 days, p < 0.001). Use of an additional preoperative dose resulted in further improvements, especially a reduction in duration of mechanical ventilation (-1.7 days versus no steroids, -1.2 days versus intraoperative steroids only, p = 0.002). Steroids were not associated with increased postoperative lactate, creatinine, or glucose levels, or odds of infection. CONCLUSIONS Intraoperative steroid use is associated with improved postoperative outcomes for children undergoing high-risk cardiac surgery, with further benefits associated with a preoperative dose.

The Berlin Heart EXCOR Pediatrics—The SickKids Experience 2004–2008

The ventricular assist device (VAD) Berlin Heart EXCOR Pediatrics was utilized at our institution since 2004 for bridging pediatric patients to cardiac transplantation or myocardial recovery. The present study reviewed our results following VAD implantation. We retrospectively reviewed patients that underwent implantation of a VAD between October 2004 and October 2008. Data collected included age at implantation, gender, weight, underlying disease, pre- and postdevice clinical status, complications, and outcome. Fifteen patients were identified (9 female and 6 male, average age: 8.8 years, range 0.3-14.8; average weight 31.1 kg, range 5.2-86.4). Indications for VAD support were dilated cardiomyopathy in 14 patients and progressing heart failure with a single ventricle physiology (bidirectional Glenn shunt) in one patient. Three patients (20%) were bridged from extracorporeal membrane oxygenation to VAD. Average support was 29 (1-108) days. Fourteen patients were on a bi-VAD, one patient (single ventricle) had single VAD support. Three patients developed mediastinal/pericardial fluid collections, requiring surgical exploration in two, and drain insertion in one. Three patients presented with neurological symptoms. In two patients, a total of three blood pumps were exchanged due to thrombus formation. No patient was weaned off the VAD; two patients (13%) died on the VAD. All surviving patients are neurologically intact at follow-up. In our experience, VAD support provides an effective means of bridging children with advanced dilated cardiomyopathy or heart failure to transplantation with a relatively small number of complications and deaths given the complexity of the patient population.

Randomized, Controlled Trial of Individualized Heparin and Protamine Management in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass

OBJECTIVES We sought to determine whether infants (younger than 1 year old) had similar clinical benefits with individualized anticoagulation management as older children and adult undergoing cardiopulmonary bypass (CPB). BACKGROUND Individualized heparin and protamine management in older children and adults undergoing CPB has been associated with improved clinical outcomes. METHODS Ninety infants younger than 1 year of age undergoing CPB were enrolled in a randomized, controlled trial comparing weight-based anticoagulation management using activated clotting time (ACT) to individualized management with Hemostasis Management System Plus. Manufacturers guidelines were followed for the first 33 patients. A modified protocol was used for the last 57 patients with adjustments for coagulation system immaturity and hemodilution on CPB. RESULTS The hemostasis management system (HMS) device consistently underestimated plasma anti-Xa levels, leading to an overestimated required heparin dose. After a blinded interim analysis revealed poor outcomes in the experimental HMS group using manufacturer guidelines, the safety committee suspended the study pending protocol modifications. The use of the HMS device following the modified protocol resulted in more stable anti-Xa levels during CPB with improved post-operative outcomes including reduced need for transfusions (71 ml/kg vs. 80 ml/kg; p = 0.003), ventilation time (33 h vs. 49 h; p = 0.04), intensive care (88 h vs. 99 h; p = 0.003), and hospital length of stay (192 h vs. 216 h; p < 0.001), compared with the weight-based protocol. CONCLUSIONS This study supports the use of the HMS device, with a modified protocol for infants younger than 1 year of age, for anticoagulation management during CPB. Clinical guidelines for the use of the HMS device should be modified for infants younger than 1 year of age.

Longer Blood Storage Is Associated With Suboptimal Outcomes in High-Risk Pediatric Cardiac Surgery

BACKGROUND The negative effects of long-term storage of allogeneic red blood cells (RBCs) on outcomes in adult cardiac surgery have been established, but evidence of a similar effect in pediatric cardiac surgery is limited. METHODS The weighted average duration of storage for RBC units used in 1,225 pediatric cardiac operations was determined. Operations were divided into high RBC use (more than 4 units or more than 150 mL/kg) or low RBC use. For both categories, associations between storage duration and surgical outcomes, adjusted for relevant patient characteristics, were evaluated. RESULTS High RBC use was associated with higher surgical complexity. Storage duration for patients who received low RBC volumes was not associated with surgical outcomes. For patients with high RBC transfusion volumes, longer storage duration (per day) was associated with higher odds of bleeding complications (odds ratio 1.029, p=0.07), renal insufficiency (odds ratio 1.085, p=0.001), higher inotrope score after surgery (12 to 24 hours +0.08, p=0.002; 24 to 48 hours +0.07, p<0.001), greater chest tube drainage (24 hours +1.5 mL/kg, p<0.001), longer postoperative hospitalization (+0.3 days p=0.02), and increased in-hospital mortality (odds ratio 1.054, p=0.03). Effects of RBC transfusions on postoperative bleeding were greatest for storage duration longer than 14 days. CONCLUSIONS The freshest RBC units available should be used for pediatric cardiac operations expected to require more than 4 units or more than 150 mL/kg of allogeneic RBC transfusions, with no units more than 14 days old being transfused whenever possible.

Left Atrial Decompression During Venoarterial Extracorporeal Membrane Oxygenation for Left Ventricular Failure in Children: Current Strategy and Clinical Outcomes

From 2005 to 2011, 23 of 178 (12.9%) patients with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) had left atrial (LA) decompression to help improve left ventricular (LV) function, LA/LV dilatation, and/or lung edema. LA decompression was achieved with LA cannulation (n = 16), surgically created adjustable atrial septal defect (n = 3), or balloon atrial septostomy (n = 4). Sixteen (70%) patients had LA decompression at the time of ECMO initiation and all had LA decompression within 12 hours of ECMO initiation. ECMO duration was 5.9 ± 4.5 days and 16 (70%) patients were successfully decannulated. Subsequent intensive care unit and hospital survival was achieved in 13 (57%) and 12 (52%) patients, respectively. Earlier timing of LA decompression appeared to be associated with a high probability of weaning from ECMO and reasonable LV functional recovery.

Challenges with heparin-based anticoagulation during cardiopulmonary bypass in children: Impact of low antithrombin activity

BACKGROUND Antithrombin is one of the main natural coagulation system inhibitors. It is potentiated by heparin, and may be a key component of heparin response, particularly in infants aged <1 year. We sought to determine the impact of baseline antithrombin activity on response to heparin and thrombin generation during cardiopulmonary bypass (CPB). METHODS Secondary analysis was performed using linear regression analyses, which combined patients from a trial of individualized versus weight-based heparin management for 90 infants aged <1 year undergoing cardiac surgery. RESULTS Mean baseline antithrombin activity was 0.69 ± 0.16 U/mL, and it was lower in neonates than in older infants (0.57 ± 0.15 vs 0.77 ± 0.12 U/mL; P < .001). Lower baseline antithrombin activity was associated with lower postheparin anti-Xa activity (EST [SE]: +0.47 (0.19) U/mL per 100 U/kg heparin; P = .01) and higher heparin doses during surgery (EST [SE]: +51 (17) U/kg per hour; P = .003). The administration of fresh frozen plasma attenuated the effect of low baseline antithrombin activity (interaction P value = .009). Patients with lower anti-Xa activity recorded during CPB had higher levels of thrombin-antithrombin complex (EST [SE]: +12.8 (4.7) ng/mL per -1 U/mL anti-Xa; P = .006); prothrombin activation fragment 1.2 (EST [SE]: +0.13 (0.07) log pg/mL per -1 U/mL anti-Xa; P = .06); and D-dimer (EST [SE]: -0.25 (0.09) log ng/mL per -1 U/mL anti-Xa; P = .009) in the postoperative period after adjustment for baseline antithrombin activity, duration of CPB, amount of fresh frozen plasma and heparin used throughout surgery in multivariable models. CONCLUSIONS Low circulating antithrombin activity is associated with lower heparin efficacy, which ultimately leads to a lower ability to suppress thrombin generation during CPB. Determination of risk factors for heparin resistance, and potentially, antithrombin replacement therapy, may individualize and improve anticoagulation treatment.

Use of a pulsatile ventricular assist device (Berlin Heart EXCOR) and an interventional lung assist device (Novalung) in an animal model.

Pulsatile ventricular assist devices (VADs) are used in pediatric patients mainly as a bridge to heart transplantation. If severe respiratory failure occurs, extracorporeal membrane oxygenation (ECMO) is currently the treatment of choice. ECMO has the potential for severe complications. Interventional lung assist (iLA) devices, e.g., the Novalung, are used in patients with isolated lung failure. This study aimed to show the feasibility of the combined use of the EXCOR VAD (10 ml and 30 ml blood pumps) and the Novalung. There were two separate experiments within this study. First, a bench test was carried out to analyze pressure and flow through both devices. Second, 10 kg and 30 kg pigs received support with the VAD and iLA in series. Pressures and flow were measured systemically before and after the iLA. Flow was unaffected by the iLA. The mean arterial pressure was reduced (mean of 13 mm Hg) by the iLA. There were no obvious difficulties observed within the interaction of VAD and iLA. The combined use of both devices is feasible and able to provide sufficient perfusion pressures. Oxygenation and CO2 clearance was effectively supported by the iLA. Patients with myocardial and respiratory failure may benefit from this setup.

Evolution of Technology, Establishment of Program, and Clinical Outcomes in Pediatric Extracorporeal Membrane Oxygenation: The “SickKids” Experience

Technological development has had a tremendous impact on the management of patients who require extracorporeal membrane oxygenation (ECMO). Team development and education are a vital component of a successful extracorporeal life support (ECLS) Program to reduce complications and subsequently improve clinical outcomes. We sought to review the evolution in technology, importance of team development and training, and report our experience at The Hospital for Sick Children, Toronto. There were a total of 576 ECMO runs in 534 patients (42 repeat ECMO runs) between January 1988 and June 2012. The use of ECMO for cardiac disease has increased in the last decade due to an expanded indication for ECMO in patients with single-ventricle physiology. Cardiac ECMO still remains a challenge in terms of survival (177/392, 45%). Although development of an ECLS program and team education facilitated extracorporeal cardiopulmonary resuscitation, clinical outcomes were not satisfactory (survival, 33%). The most common complications were hemorrhagic (13.8%), followed by renal (10.6%) and pulmonary dysfunction (6.9%). Advances in technology made management during ECMO safer, and the mechanical complications related to the ECMO system were 6.1%, including circuit changes due to thrombus formation, cannula repositioning, or optimization of size.