Tom N. Hoel

Evaluation of oxygenators and centrifugal pumps for long-term pediatric extracorporeal membrane oxygenation:

Objective : Two extracorporeal membrane oxygenation (ECMO) circuits for children under 10 kg were evaluated and compared for plasma leakage, hemolysis, blood transfusions, and durability. Methods: Group A (n = 20) was supported by ECMO circuits with the Minimax oxygenator and the Biomedicus centrifugal pump. Group B (n = 10) was supported by ECMO circuits with the Lilliput 2 ECMO oxygenator and the Rotaflow centrifugal pump. Results: ECMO circuit durability, as measured by oxygenator lifespan, was significantly better in Group B than in Group A (p = 0.04). There was significantly lower hemolysis, measured by plasma free hemoglobin, in Group B (p = 0.019), and patients in Group B had significantly less need for antithrombin III transfusion (p = 0.004). No plasma leakage was observed in Group B oxygenators, but plasma leakage was observed in all Group A oxygenators. Conclusion: The combination of a Rotaflow centrifugal pump and Lilliput 2 ECMO oxygenator in pediatric ECMO circuits improved durability and reduced circuit-induced hemolysis. This improvement may be due to the low priming volume, the oxygenators plasma leakage resistance, the suspended rotor of the centrifugal pump, or a combination of these factors. Perfusion (2007) 22, 323—326.

Syndecan-1 plasma levels during coronary artery bypass surgery with and without cardiopulmonary bypass

The glycocalyx covering the endothelium is shed during ischemia and reperfusion. The shedding is accompanied by increased levels of the glycocalyx component syndecan-1 in the circulation. Our aim was to compare plasma levels of syndecan-1 in patients undergoing coronary artery bypass grafting (CABG), with or without the use of cardiopulmonary bypass (CPB). Syndecan-1 plasma concentrations were measured in patients undergoing CABG on-pump (n = 22) or off-pump (n = 22). The syndecan-1 concentration increased significantly from 29.5 ± 4.6 ng/mL at baseline to 98.7 ± 9.8 ng/mL (p < 0.01) after the start of CPB or 30 minutes after the induction of anesthesia in the off-pump group. There were no significant differences in peak syndecan-1 plasma concentrations between on-pump and off-pump patients. Plasma levels of syndecan-1 increased significantly during CABG, with or without the use of CPB. There were no significant differences in syndecan-1 concentrations in the two groups.

Achievements in Congenital Heart Defect Surgery: A Prospective, 40 Year Study of 7038 Patients

Background— This article presents an update of the results achieved by modern surgery in congenital heart defects (CHDs) over the past 40 years regarding survival and the need for reoperations, especially focusing on the results from the past 2 decades. Methods and Results— From 1971 to 2011, all 7038 patients <16 years of age undergoing surgical treatment for CHD at Rikshospitalet (Oslo, Norway) were enrolled prospectively. CHD diagnosis, date, and type of all operations were recorded, as was all-cause mortality until December 31, 2012. CHDs were classified as simple (3751/7038=53.2%), complex (2918/7038=41.5%), or miscellaneous (369/7037=5.2%). Parallel to a marked, sequential increase in operations for complex defects, median age at first operation decreased from 1.6 years in 1971 to 1979 to 0.19 years in 2000 to 2011. In total, 1033 died before January 1, 2013. Cumulative survival until 16 years of age in complex CHD operated on in 1971 to 1989 versus 1990 to 2011 was 62.4% versus 86.9% (P<0.0001). In the comparison of patients operated on in 2000 to 2004 versus 2005 to 2011, 1-year survival was 90.7% versus 96.5% (P=0.003), and 5-year cumulative survival was 88.8% versus 95.0% (P=0.0003). In simple versus complex defects, 434 (11.6%) versus 985 (33.8%) patients needed at least 1 reoperation before 16 years of age. In complex defects, 5-year cumulative freedom of reoperation among patients operated on in 1990 to 1999 versus 2000 to 2011 was 66% versus 73% (P=0.0001). Conclusions— Highly significant, sequential improvements in survival and reductions in reoperations after CHD surgery were seen. A future challenge is to find methods to reduce the need for reoperations and further reduce long-term mortality.Background— This article presents an update of the results achieved by modern surgery in congenital heart defects (CHDs) over the past 40 years regarding survival and the need for reoperations, especially focusing on the results from the past 2 decades. Methods and Results— From 1971 to 2011, all 7038 patients <16 years of age undergoing surgical treatment for CHD at Rikshospitalet (Oslo, Norway) were enrolled prospectively. CHD diagnosis, date, and type of all operations were recorded, as was all-cause mortality until December 31, 2012. CHDs were classified as simple (3751/7038=53.2%), complex (2918/7038=41.5%), or miscellaneous (369/7037=5.2%). Parallel to a marked, sequential increase in operations for complex defects, median age at first operation decreased from 1.6 years in 1971 to 1979 to 0.19 years in 2000 to 2011. In total, 1033 died before January 1, 2013. Cumulative survival until 16 years of age in complex CHD operated on in 1971 to 1989 versus 1990 to 2011 was 62.4% versus 86.9% ( P <0.0001). In the comparison of patients operated on in 2000 to 2004 versus 2005 to 2011, 1-year survival was 90.7% versus 96.5% ( P =0.003), and 5-year cumulative survival was 88.8% versus 95.0% ( P =0.0003). In simple versus complex defects, 434 (11.6%) versus 985 (33.8%) patients needed at least 1 reoperation before 16 years of age. In complex defects, 5-year cumulative freedom of reoperation among patients operated on in 1990 to 1999 versus 2000 to 2011 was 66% versus 73% ( P =0.0001). Conclusions— Highly significant, sequential improvements in survival and reductions in reoperations after CHD surgery were seen. A future challenge is to find methods to reduce the need for reoperations and further reduce long-term mortality. # CLINICAL PERSPECTIVE {#article-title-36}

Single-center 50 years’ experience with surgical management of tetralogy of Fallot

OBJECTIVE The aim of this study was to evaluate the long-term outcome of total repair for tetralogy of Fallot. We aimed to characterize late survival and the time-related risk of late reoperation. METHODS Operative protocols, patient records, and the database of the department were evaluated from 1951 until 2008. The official death registry of Norway was used for follow-up. Of the patients identified, the follow-up was 99.6% complete. RESULTS A total of 627 patients were studied. Of these, 570 could be identified for follow-up. There were a total of 41 early and 30 late deaths. The total early (including palliative procedures) mortality was 7.2% and total late mortality was 7.9%. However, during the last 10 years, no early mortality has been observed following repair. A total of 264 patients underwent some form of palliative procedure as their first treatment, and 541 patients had a reparative procedure performed, with an early mortality of 31 (5.7%). In patients subjected to a reparative procedure, there was no difference in freedom from death or reoperation following primary repair versus primary palliation. The use of transannular patch was associated with a highly significant risk of reoperation. CONCLUSIONS Surgical treatment of the tetralogy of Fallot and related congenital cardiac malformations has good long-term prognosis. In this cohort of patients, more than one-third required additional procedures later on, and, in some cases, as many as four additional surgeries. Palliative procedures followed by repair do not influence survival or reoperation-free survival. There are no differences between transatrial versus transventricular repair on survival or re-repair. Any transannular incision increases the risk of re-repair, but does not influence long-time survival. There is an almost linear decrease in reoperation-free survival following any type of repair of tetralogy of Fallot, even for as long as 50 years since the first procedure.

Biomarker Profile in Off-Pump and On-Pump Coronary Artery Bypass Grafting Surgery in Low-Risk Patients

BACKGROUND The purpose of this study was to investigate the cytokine and chemokine profile in low-risk patients undergoing off-pump and on-pump coronary artery bypass grafting (CABG) surgery by use of a broad panel of cytokines and chemokines. METHODS Eight consecutive blood samples were obtained from patients enrolled into a prospective, randomized study comparing off-pump and on-pump CABG in a low-risk population. Eleven patients from each group were randomly selected for analysis of 25 different cytokines and chemokines using multiplex technology. Data were compared using two-way repeated measures analysis of variance. RESULTS Of the 25 biomarkers analyzed, 11 were not detected while 14 increased significantly in both groups. Only three mediators, eotaxin, macrophage inflammatory protein (MIP)-1beta, and interleukin (IL)-12 were significantly different between the two groups, increasing more in the on-pump than in the off-pump group (p < 0.001, p < 0.01, and p < 0.05, respectively). There was a marked, comparable increase in the concentrations of the cytokines IL-6, IL-10, IL-15, and IL-1Ra as well as the chemokines inducible protein (IP)-10, monokine induced by interferon gamma (MIG), monocyte chemoattractant protein 1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES) in both groups (p < 0.001 for all). There was only a modest, but still statistically significant, increase in IL-8, tumor necrosis factors alpha, and IL-2R, without any intergroup differences. When corrected for hemodilution the production of the antiinflammatory biomarkers IL-1Ra and IL-10 were significantly higher in the on-pump group (p < 0.001 for both). CONCLUSIONS The cytokine and chemokine production profile of the inflammatory response associated with CABG is largely similar using the off-pump and on-pump techniques in low-risk patients, but slightly higher concentrations of eotaxin, MIP-1beta, and IL-12 were found in the on-pump group.

Off-pump cardiac surgery abolishes complement activation

Background . This prospective randomized study compared the inflammatory response in patients undergoing elective on-pump and off-pump coronary artery bypass grafting. Patients and methods. Forty-four patients undergoing elective coronary artery bypass grafting were recruited with 22 patients randomized to on-pump heart surgery and 22 patients to off-pump coronary bypass surgery. Plasma levels of C3bc, the terminal SC5b-9 complement complex, myeloperoxidase, β -thromboglobulin and prothrombin fragment F1 + 2 were measured before the operation, intraoperatively, at termination of the operation, and two hours post-operatively. Results. Complement was markedly activated in the on-pump group as indicated by a significant increase in C3bc and SC5b-9 (p < 0.001 for both), whereas no complement activation was seen in the off-pump group (p = 0.001 between the groups). In contrast, both groups showed significant activation of neutrophils, platelets and coagulation, as indicated by an early increase in myeloperoxidase and a post-operative increase in β-thromboglobulin and F1 + 2, respectively. Notably, there were no inter-group differences with regard to neutrophil and platelet activation, whereas coagulation activation was more pronounced in the off-pump group (p < 0.01). Conclusions. Off-pump surgery completely eliminated the heart-lung machine-induced complement activation. Neutrophils and platelets were equally activated in both groups, whereas coagulation was enhanced post-operatively in the off-pump group. Perfusion (2007) 22, 251—256.

Comparable biocompatibility of Phisio- and Bioline-coated cardiopulmonary bypass circuits indicated by the inflammatory response

Background: The biocompatibility of cardiopulmonary bypass surfaces has been improved by heparin and polymer surface modifications. The present study compared the effect of two such coatings on the inflammatory reactions after open heart surgery. Methods:Thirty patients undergoing elective heart surgery were randomly assigned to receive one of two types of coated circuits: Bioline (n=15) or phosphorylcholine (Phisio, n=15). The platelet and leukocyte counts, neutrophil activation (myeloperoxidase), complement activation (C3a and TCC), concentrations of lactate dehydrogenase, 27 cytokines (including interleukins, chemokines and growth factors), thrombin-antithrombin complexes, and the endothelial cell marker syndecan-1 were analyzed at five predetermined time points until 24 hrs post operatively. Results: Most measurements were comparable in both groups. However, myeloperoxidase was significantly higher in the Bioline group (p < 0.001). Postoperative lactate dehydrogenase concentrations were significantly higher in the Phisio group (p<0.01) and the maximal concentration of thrombin-antithrombin complexes 2 hours postoperatively tended to be higher in the Phisio group (p=0.08), consistent with a longer aortic cross-clamp and cardiopulmonary bypass time. Conclusions: The two circuits exhibited a comparable degree of in vivo biocompatibility.

Pediatric Coronary Artery Revascularization: A European Multicenter Study

BACKGROUND We sought to evaluate the hospital and midterm results of different surgical revascularization techniques in pediatric patients within the European Congenital Heart Surgeons Association. METHODS From 1973 to 2011, 80 patients from 13 European Congenital Heart Surgeons Association centers underwent 65 pediatric coronary artery bypass grafting (PCABG) and 27 other coronary artery procedures (OCAP; 12 patients had combined PCABG and other coronary artery procedures). Excluded were patients with Kawasaki disease. Median age at the time of coronary procedure was 2.3 years (range, 2 days to 16.9 years); 33 patients (41.2%) were younger then 12 months. An emergency procedure was necessary in 34 patients (42.5%). RESULTS Twelve patients (15%) died in the hospital; age at surgery (p=0.02) and the need for an emergent procedure (p=0.0004) were related to hospital mortality. Median follow-up time was 7.6 years (range, 0.9 to 23 years). There were 3 late cardiac deaths, all after a median time of 4 years (range, 9 months to 8.8 years) after PCABG. Fourteen patients (20.5%) presented with symptoms, including congestive heart failure (n=10) and angina (n=4), that were significantly associated with a low ejection fraction (p<0.001) and the presence of moderate or severe mitral valve regurgitation (p=0.0003). Six patients underwent a reintervention for impaired myocardial perfusion; all of them had a stenotic or atretic PCABG (p=0.001), and the majority were symptomatic (5 of 6 patients; 83.3%; p=0.001). CONCLUSIONS Both PCABG and other coronary artery procedures are suitable surgical options in pediatric patients with impaired myocardial perfusion, which increases operative and midterm survival. Such population of patients needs to be followed for life to prevent and treat any possible cause of further myocardial ischemia.

Comparison of a Duraflo II-coated cardiopulmonary bypass circuit and a trillium-coated oxygenator during open-heart surgery:

Background: Cardiopulmonary bypass (CPB) evokes a systemic inflammatory response. In attempting to improve the biocompatibility of the equipment, various methods to coat the inner surfaces of the CPB systems have been developed. The present study compares a Trillium Biopassive surface-coated Affinity oxygenator with a Duraflo II totally heparin-coated CPB system. Methods: Low-risk patients admitted for primary coronary artery bypass grafting or aortic valve replacement were randomized to operation using the Trillium- or the Duraflo II-coated setups. Heparin concentration, complement activation (C3bc activation products and terminal complement complex (TCC)), platelet activation (platelet numbers and beta-thromboglobulin (BTG)), leukocyte activation (leukocyte numbers and myeloperoxidase (MPO)), coagulation (thrombin/antithrombin complexes (TAT)) and fibrinolytic activity (plasmin/a2-antiplasmin complexes (PAP)) were measured during CPB and two hours postoperatively. Results: Platelet counts decreased during CPB, without significant intergroup differences. The median BTG concentration increased moderately in both groups and were slightly higher in the Trillium group during CPB (p B-0.05), but not postoperatively. Complement activation products (C3bc and TCC), leukocyte counts, MPO, TAT and PAP activity showed no differences between the two groups. Conclusions: There were small differences in the inflammatory response between the two extracorporeal circulation devices compared in this study.

In vitro evaluation of PHISIO-coated sets for pediatric cardiac surgery

Objectives. Phosphorylcholine coated cardiopulmonary bypass (CPB) circuits for children have been available for some years, but conflicting results regarding the inflammatory response have been reported. Accordingly, we aimed to investigate the effect of phosphorylcholine coating on the inflammatory response. Design. Ten coated and nine uncoated pediatric CPB sets were tested in an in vitro CPB circuit model. The inflammatory response was assessed by serial assays of hemoglobin, hematocrit, leukocyte counts, platelet counts, activation of the complement system, activation of platelets measured as β-thromboglobulin, activation of neutrophils measured as myeloperoxidase, activation of coagulation measured as prothrombin fragments 1+2, assessment of hemolysis measured as lactate dehydrogenase, and a panel of seven cytokines. Samples were obtained at baseline and after 15, 30, 60 and 120 minutes. Results. There were no significant differences between the phosphorylcholine coated circuits and the uncoated circuits for any of the parameters during the observation period, although a potentially beneficial effect on platelets could not be ruled out. Conclusions. Phosphorylcholine coating of CPB equipment did not exert any beneficial effect on the inflammatory markers monitored.