Elevated levels of trypsinogen-2 and trypsin-2-alpha1-antitrypsin in sera of infants and children after cardiac surgery.

Acute pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass but amylase is not a reliable marker in infants. We evaluated whether the serum concentrations of trypsinogen-2 and trypsin-2-alpha1-antitrypsin (AAT) can be used to study disturbances in pancreatic function in children and infants undergoing cardiac surgery. The study comprised 21 infants < 1 year and 25 children aged 1-16 years undergoing cardiopulmonary bypass at the Children's Hospital, Helsinki University Central Hospital. Consecutive serum samples were taken before surgery, at 12 h, 1, 2 and 3 days after surgery, and before discharge from the hospital. A moderate increase in trypsinogen-2 and trypsin-2-AAT in serum was found in more than two-thirds of the patients. On day 3, there was a 4.3-fold mean increase (CI 95% 2.8-6.5) in trypsinogen-2 and a 2.4-fold mean increase (CI 95% 1.8-3.1) in trypsin-2-AAT. In 4 patients trypsinogen-2 was elevated by more than 20-fold. One patient had clinical pancreatitis, but there were no clinical signs of pancreatitis in the other three patients. The changes in trypsinogen-2 and trypsin-2-AAT were similar in infants and children. The moderate increase in the serum concentrations of trypsinogen-2 and trypsin-2-AAT after cardiac surgery in the absence of signs of pancreatitis may be due to a subclinical pancreatic disturbance, but it could also be caused by an inflammatory response and expression of extrapancreatic trypsin. Contrary to amylase, trypsinogen-2 is expressed in the pancreas of infants.

Evaluation of the relationship between preoperative risk scores, postoperative and total length of stays and hospital costs in coronary bypass surgery.

OBJECTIVES: Several risk indices have been developed for the prediction of postoperative mortality and morbidity in coronary artery bypass operations, in which the risk scores are currently recorded as routine praxis. The aim of the present study was to determine whether the risk scores can be used to predict the hospital (LOS) and postoperative (POS) lengths of stay and total costs among coronary artery bypass graft (CABG) patients. METHODS: All first-time CABG patients (n=2104) treated at Helsinki University Central Hospital during 1997-1998 were preoperatively scored using the Cleveland Clinic preoperative model. A multivariate analysis was used to evaluate the effects of the risk scores on the LOS and POS and total costs. RESULTS: The mean preoperative risk score for the patients was 1.69. The increase in preoperative risk score was associated with an increase in the LOS (0.8 days by point), and POS (with 0.55 days by point). An age over 74 years increased the LOS by an extra day. The mean total cost for the CABG procedure was 8750 euros (SD 4430 euros). The costs increased as the risk score increased. Compared with the zero risk score, a score value of 2 was associated with a 1300 euros increase in total cost and a score value of over 6 was associated with an over 7000 euros cost increase. On average, the costs increased by 6980 euros (80%) for one major complication and by 935 euros (10%) in the elderly (>74 years of age). CONCLUSIONS: The results show that increasing risk scores were associated with longer postoperative hospital lengths of stay (POS and LOS) and with increased total costs. An age over 74 years appears to be an independent risk factor in increased POS, LOS and total cost. These results may help to estimate the impact of the preoperative risk profile on the resource requirement in CABG surgery.

Delayed impairment of cerebral oxygenation after deep hypothermic circulatory arrest in children.

BACKGROUND: Clinical studies of deep hypothermic circulatory arrest (DHCA) have focused only on the immediate postoperative period. However, experimental findings suggest impairment of cerebral oxygenation at 2 to 8 hours after reperfusion. METHODS: In 10 children who had DHCA for heart operations, transcerebral differences of hemoglobin oxygen saturation and plasma hypoxanthine, xanthine, and lactoferrin concentrations were measured in concurrently obtained cerebral venous, arterial, and mixed venous samples up to 10 hours postoperatively. RESULTS: Compared with preoperative levels (57% +/- 7%), cerebral venous oxygen saturation was not significantly reduced until 2 hours (44% +/- 6%) and 6 hours (42% +/- 5%) after DHCA (p < 0.05). A statistically significant transcerebral (ie, cerebral vein versus artery) concentration difference of hypoxanthine was observed at 30 minutes (3.6 +/- 0.9 micromol/L), 1 hour (3.4 +/- 1.1 micromol/L), and 2 hours (3.1 +/- 0.8 micromol/L) after DHCA but not preoperatively (0.4 +/- 0.2 micromol/L). A transcerebral concentration difference of lactoferrin occurred 30 minutes after DHCA (196 +/- 70 microg/mL) but not preoperatively (16 +/- 20 microg/mL). CONCLUSIONS: Cerebral venous oxygen saturation of hemoglobin decreased as late as 2 to 6 hours after DHCA, in association with impaired cerebral energy status. Neutrophil activation in the cerebral circulation occurred 30 minutes after reperfusion.

Successful liver transplantation after induction chemotherapy in children with inoperable, multifocal primary hepatic malignancy.

BACKGROUND: The prognosis for primary epithelial liver tumor in children in whom radical surgery cannot be performed after chemotherapy is poor. Orthotopic liver transplantation has resulted in mortality up to 50%, largely as a result of problems in determining the criteria for transplantation. METHODS: We report results on liver transplantation for primary epithelial liver malignancy in five children (mean age at transplantation: 6.0 years). Only patients with inoperable residual tumor in the liver after four cycles of multidrug chemotherapy, but without extrahepatic infiltration or metastases, were considered eligible for transplantation. RESULTS: Mean follow-up was 4.6 years. Patient and graft survival was 100%, with no signs of residual or de novo malignancy. CONCLUSION: In children with inoperable primary liver malignancy with no extrahepatic tumor growth, orthotopic liver transplantation has an excellent outcome.

Graft function 5-7 years after renal transplantation in early childhood.

BACKGROUND: Low recipient age is still a risk factor for graft failure after kidney transplantation (Tx). Detailed prospective reports on long-term graft function in small children after renal Tx are still lacking. METHODS: Forty-nine kidney allograft recipients who received transplants before the age of 5 years were followed prospectively. The most common disease was congenital nephrotic syndrome of the Finnish type. Twenty patients were recipients of living related donors (LRD), and 29 were cadaveric kidney (CAD) recipients. All patients received triple immunosuppression. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), sodium, urate, and potassium handling, and concentrating capacity were studied for up to 7 years after Tx. RESULTS: Patient survival 7 years after Tx was 100% for LRD and 96% for CAD recipients. Graft survival was 94% for LRD and 79% for CAD recipients (P=NS) and 89% and 83% for children >2 years and <2 years of age at Tx, respectively (P=NS). Five years after Tx, GFR was 70 vs. 64 and ERPF was 380 vs. 310 ml/min/1.73 m2 for LRD and CAD recipients, respectively (P=NS). Mean absolute GFR remained stable. GFR was lower in children who received transplants at <2 years than in children who received transplants at >2 years of age, 54 vs. 75 ml/min/1.73 m2 (P=0.02). Sodium handling remained intact, but hyperuricemia was seen in 43-67%; 17-33% showed abnormal handling of potassium; and most patients had a subnormal concentrating capacity. CONCLUSIONS: Excellent long-term graft survival and good graft function can be achieved with triple immunosuppression, even in young CAD kidney recipients.

Long-term follow up of renal function and histology after renal allograft transplantation in early childhood.

Survival rates, renal function, and histopathology were evaluated in 49 prospectively followed patients transplanted under 5 years of age at our center. Most patients (84%) suffered from congenital nephrosis of the Finnish type. Triple immunosuppression with cyclosporine administered in three daily doses to pre-school children was used. Patient survival 7 years after transplantation was 98% and graft survival 88%. All graft losses were due to post-transplantation nephrosis. The proportion of pathological findings in the follow-up biopsies did not change substantially with time. Five years after transplantation, 47% showed a normal histology and after 7 years this rose to 67%. Mean glomerular filtration rate (GFR) was 68 and 55 ml min per 1.73 m2 5 years and 7 years, respectively, after transplantation. The decline in GFR with time was significant. We conclude that good long-term results can be achieved with individually tailored triple immunosuppression in the youngest age group, even with cadaveric donors.

Direct reconstruction of the pulmonary artery during the arterial switch operation: an interesting surgical option with excellent hemodynamic results.

BACKGROUND: In transposition of the great arteries, reconstruction of the neo-pulmonary artery is a challenging surgical detail during the arterial switch procedure. We present early and midterm clinical and hemodynamic results of a direct reconstruction of the pulmonary artery avoiding prosthetic and autologous material. METHODS: Between 1990 and June 1996, a total of 189 patients underwent the arterial switch procedure because of D-transposition of the great vessels. Of them, 47 underwent direct pulmonary artery reconstruction. Mean age at operation was 5.2+/-4.1 days and mean weight was 3.75+/-0.85 kg. Simple transposition of the great arteries was present in 13, transposition of the great arteries plus ventricular septal defect in 27, and more complex forms of transposition of the great arteries in 7 patients. The great vessels were side-by-side in 4 patients and in the anteroposterior position in 43 patients. The technique of direct pulmonary reconstruction includes extensive mobilization of both pulmonary artery branches into the hilum, posterior incision of the mean pulmonary artery into the bifurcation, and resuspension of the posterior commissure of the neo-pulmonary valve. A large anastomosis without any tension is then performed, using the anterior remnant aortic sinus of Valsalva to fit out the expected size of the neo-pulmonary artery. RESULTS: Early mortality was 8.5% (4/47) in this particular group of patients. Postoperative echocardiography was performed before hospital discharge, 3 to 6 months postoperatively, and after a mean follow-up of 24 months. Of the 43 survivors, 37 patients had a pressure gradient across the pulmonary valve of less than 15 mm Hg. Mild pulmonary stenosis (pressure gradient of 15 to 30 mm Hg) was present in 4 and more severe supravalvar stenosis (pressure gradient > 30 mm Hg) in 2 patients. After a mean follow-up of 36 months, there was one redo operation to enlarge the right ventricular outflow tract. CONCLUSIONS: Direct reconstruction of the neo-pulmonary artery-avoiding autologous pericardium and prosthetic material-may represent an interesting option during the arterial switch operation when the great vessels lie in the anteroposterior position. This technique is simple, and the hemodynamic midterm results are very favorable. The incidence of postoperative supravalvar pulmonary stenosis is low, and there may be considerable potential for unlimited tissue growth.

Paediatric kidney transplantation.

Renal transplantation is the optimal form of renal replacement therapy leading to substantial improvement in the quality of life. It has rapidly become the standard treatment for end-stage renal disease in children. However, despite impressive short-term results significant long-term problems remain unsolved. Because of the lack of effective treatment for chronic rejection and common recipient noncompliance, allograft half-life has not improved significantly during the last decade. A paediatric recipient is likely to need several retransplantations in adulthood. Moreover, the immunosuppressive drugs used today have potentially serious side-effects including nephrotoxicity and de novo malignancy. These are especially relevant for paediatric recipients who will continue to receive therapy for several decades. Most therapeutic protocols used for children are derived from those used for adults. However, the metabolic differences between an adult and a growing and developing paediatric transplant recipient are not always adequately appreciated before these new therapies are initiated. In the near future, we are likely to see new and more efficient drugs become available. It is important that we try to understand their properties in children and use them and our current arsenal on an individual basis aiming at optimal graft survival but also at avoiding unnecessary adverse effects.

Amrinone versus dopamine-nitroglycerin after reconstructive surgery for complete atrioventricular septal defect.

OBJECTIVES: To compare the effectiveness and safety of amrinone and a combination of dopamine and nitroglycerin in infants after reconstructive surgery for congenital heart disease. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Thirty-two infants with complete atrioventricular septal defect. INTERVENTIONS: Amrinone loading dose, 2 mg/kg, followed by a maintenance infusion, 7.5 micrograms/kg/min, was given to 17 infants before separation from cardiopulmonary bypass. The remaining 15 patients received a combination of dopamine, 5 micrograms/kg/min, and nitroglycerin, 1 microgram/kg/min. MEASUREMENTS AND MAIN RESULTS: The circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (2.5 +/- 0.7 L/min/m2) compared with the dopamine-nitroglycerin group (2.0 +/- 0.6 L/min/m2, mean +/- SD). The pulmonary blood flow index in the amrinone group was higher (2.9 +/- 0.6 L/min/m2) than in the dopamine-nitroglycerin group (2.2 +/- 0.6 L/min/m2); no significant difference was noted in the mean pulmonary artery pressure. The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.41 +/- 0.07) compared with the amrinone group (0.34 +/- 0.08). Despite lower platelet counts in the amrinone group, no hemorrhagic complications were seen in any patient. CONCLUSIONS: With this dosage regimen, amrinone provides a higher cardiac output, more favorable oxygen dynamics, and lower pulmonary vascular resistance than dopamine and nitroglycerin.

Malformation and stenosis of the cricoid cartilage in association with Larsen's syndrome.

Three patients with the typical features of Larsen's syndrome are described. All three developed severe respiratory symptoms caused by a congenital subglottic stenosis. Tracheotomy and treatment of the stenosis by means of laryngotracheoplasty resulted in complete collapse of the cricoid cartilage and the proximal tracheal skeleton. Lack of rigidity of the laryngeal and tracheal cartilages in patients with Larsen's syndrome could well be responsible for this failure. Surgical treatment consisted of resection of the stenotic and collapsed areas and end-to-end anastomosis. This therapy was eventually successful in all three patients.

Kidney function in cyclosporine-treated pediatric heart transplant recipients.

BACKGROUND: End-stage kidney disease may develop in 1% to 3% of cyclosporine-treated heart transplant recipients, and most patients show a decreased glomerular filtration rate. There are little data on kidney function in pediatric recipients, although good function is needed for their optimal development. METHODS: Kidney function was prospectively investigated in 10 children receiving triple immunosuppression (cyclosporine, azathioprine, methylprednisolone) during the first 18 months after heart transplantation. The early cyclosporine trough level target was 300 to 500 micrograms/L and 100 to 200 micrograms/L after the first year. 51Chromium-ethylenediamine tetraacetic acid, para-amino hippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were obtained from four patients after 18 months. RESULTS: Heart function was good in all patients. Six patients (60%) remained rejection-free at 18 months. The mean glomerular filtration rate was 92.4 ml/min/1.73 m2 before transplantation, increased to 115 by 6 months (p < 0.05), and thereafter remained stable. The mean renal plasma flow was 487 ml/min/1.73 m2 after 18 months. Hypertension was seen in all patients at discharge but in only one at 18 months. Mild hyperuricemia was the most common sign of tubular dysfunction occurring in five patients at discharge but in only two patients at 18 months. The result of kidney histopathologic study was normal in three of four patients, and cyclosporine nephrotoxicity was not diagnosed. CONCLUSIONS: Triple immunosuppression with cyclosporine adequately protects the graft against acute rejection. It is compatible with normal glomerular function and leads to only minor tubular disturbances.

Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations.

Fibrinolysis and coagulation were studied in 10 neonates undergoing cardiac operations for congenital heart defects. Coagulation was activated during cardiopulmonary bypass as evidenced by highly increased prothrombin fragment 1 + 2 levels compared with preoperative values. Prothrombin fragment 1 + 2 levels remained elevated until postoperative day 3. Unlike coagulation, fibrinolysis was not activated during cardiopulmonary bypass but did show late activation on postoperative day 3, as evidenced by elevated levels of the fibrin degradation product D-dimer. Lack of fibrinolytic activation during bypass and its appearance on postoperative day 3 were partly explained by changes observed in tissue plasminogen activator and its inhibitor. During bypass, levels of tissue plasminogen activator and its inhibitor increased by 3.4-fold and 3.2-fold, respectively. In the postoperative period, levels of plasminogen activator inhibitor normalized rapidly whereas tissue plasminogen activator remained elevated, resulting in late fibrinolytic activation on postoperative day 3. In accordance with elevated prothrombin fragment 1 + 2, platelet count, antithrombin III, protein C, prothrombin, and factor VII were decreased on postoperative day 2, indicating ongoing consumptive coagulopathy. Nine patients had antithrombin III and six had protein C levels below age-specific normal ranges, consistent with an acquired deficiency state. Three had central venous thrombosis by postoperative day 4 or 5. In all three, thrombosis was preceded by antithrombin III deficiency, protein C deficiency, and highly elevated plasminogen activator inhibitor (3.7 to 37 times the mean of the other patients) on postoperative days 1 to 3. In conclusion, cardiopulmonary bypass in neonates caused rapid and profound alterations in the coagulation and fibrinolytic systems and initiated consumptive coagulopathy lasting until at least postoperative day 3. Thrombophilic abnormalities in antithrombin III, protein C, and fibrinolysis were frequently found and were associated with serious thrombotic complications.

Hyperamylasemia after cardiac surgery in infants and children.

OBJECTIVE: This study was conducted to clarify the incidence of hyperamylasemia after cardiac surgery in infants and children. DESIGN AND PATIENTS: 186 infants and children operated on at Children's Hospital. Helsinki, during an 11-month period were enrolled in the study. Serum samples were taken before and on 3 consecutive days after cardiac surgery at the intensive care unit and before discharge from the hospital. MEASUREMENTS: We measured serum total amylase and serum pancreatic amylase with two different assays (1) reduction of salivary amylase from total amylase activity and (2) measurement of mass concentration with monoclonal antibodies. RESULTS: Preoperative values for both total amylase and pancreatic isoenzymes were strongly age-related. At least one of the three tests showed postoperative hyperamylasemia (> +/- 2 SD above starting values of the age group and maximal value > 3 times the individual starting value) in 64/186 (34%) patients. 22/186 (12%) patients had abnormal results in all assays. A more than tenfold rise in pancreatic amylase, suggesting pancreatitis, was found in 14 patients (8%). Mortality was 21% in this subgroup, but 5% in the rest of the patients. Hyperamylasemia was more common after 1 year of age, and after open-heart surgery, especially homograft implantation or cardiac transplantation. CONCLUSIONS: Hyperamylasemia is a common finding after cardiac surgery in pediatric patients. Amylase isoenzyme measurements are needed for clinical decision making. Age-group-related reference values are mandatory for the right interpretation of amylase values.

Prolonged granulocyte activation, as well as hypoxanthine and free radical production after open heart surgery in children.

OBJECTIVE: To investigate granulocyte activation, as well as hypoxanthine and free radical production in children during the first day after cardiopulmonary bypass. DESIGN: A prospective study of pediatric patients undergoing either cardiac surgery with a cardiopulmonary bypass or thoracotomy and extracardiac vascular surgery not requiring a cardiopulmonary bypass. SETTING: Operative and intensive care units, Children's Hospital, University of Helsinki, Finland. PATIENTS: Seven consecutive patients undergoing elective correction of a ventricular septal defect and six patients undergoing extracardiac surgery for ligation of a patent ductus arteriosus or repair a coarctation of the aorta. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of myeloperoxidase (140-334 micrograms/l preoperatively, 460-1692 micrograms/l at 0.2 h after declamping, 471-1386 micrograms/l at 0.5 h after declamping) and lactoferrin (77-258 micrograms/l preoperatively, 533-1783 at 0.2 h, 404-1482 micrograms/l at 0.5 h) as markers of granulocyte activation, and hypoxanthine (0-5.7 mumol/l preoperatively, 4.3-17.0 mumol/l at 0.2 h, 6.5-17.9 mumol/l at 0.5 h) increased in a biphasic manner at 0.2-0.5 h and 6-10 h postoperatively (all p < 0.05). Expired ethane, as an index of free radical activity, increased at 10 h postoperatively (36-119 pmol/kg per min preoperatively, 72-152 pmol/kg per min, p < 0.005). CONCLUSION: Granulocyte activation, and hypoxanthine and free radical production occur at least 10 h after cardiopulmonary bypass. In children undergoing open heart surgery, attempts to reduce free radical activity should be extended to the postoperative period.

-Aneurysm of the pulmonary artery and pulmonary artery hypertension 22 years after Mustard reversal operation in transposition of great vessels-. / Aneurysma der Pulmonalarterie und pulmonalarterielle Hypertonie 22 Jahre nach Mustard-Umkehroperation bei Transposition der grossen Gefässe.

An increasing number of patients with transposition of great arteries reaches adult age after an atrial redirection operation. The well known late sequelae of the Mustard and Senning operations include supraventricular brady-tachyarrhythmias, dilatation and failure of the systemic ventricle, severe tricuspid valve incompetence, obstruction of either the systemic or pulmonary venous return as well as left ventricular outflow tract obstruction, and baffle leaks. The case of a 26-year-old woman with a rarer postoperative course, namely severe aneurysmal dilatation of the pulmonary artery and pulmonary arterial hypertension 22 years after a Mustard operation is described. The pros and contras of the available therapeutic alternatives are discussed.

Regional generation of free oxygen radicals during cardiopulmonary bypass in children.

Studies on free radical generation during cardiopulmonary bypass have focused mainly on the heart and the lungs. However, low pumping pressure, nonpulsatile perfusion, and hypothermia affect the entire circulation, resulting in decreased splanchnic blood flow, increased intestinal permeability, and endotoxemia. To evaluate regional phenomena, we studied 16 children undergoing cardiopulmonary bypass. Free radical production, granulocyte activation, and hypoxanthine metabolism were assessed separately in the circulations drained by the inferior and superior venae cavae, as well as in the oxygenator. Three minutes after the onset of cardiopulmonary bypass, significant gradients between the inferior vena cava and the arterial line of the oxygenator existed in malondialdehyde (+0.60 +/- 0.12 mumol/L, lactoferrin (+18.21 +/- 7.65 micrograms/L), myeloperoxidase (+53.75 +/- 16.50 micrograms/L), hypoxanthine (-0.62 +/- 0.15 mumol/L), and urate (+8.87 +/- 4.03 mumol/L). These gradients decreased in parallel with decreasing body temperature. Except for a transient gradient in malondialdehyde at 3 minutes after the onset of cardiopulmonary bypass (+0.23 +/- 0.08 mumol/L), no changes were detected between the superior vena cava and the arterial line. In the oxygenator, granulocyte activation was observed only after aortic declamping. We conclude that during cardiopulmonary bypass, significant free radical generation, granulocyte activation, hypoxanthine elimination, and urate production take place in the region drained by the inferior vena cava. In the oxygenator, granulocyte activation occurs only after aortic declamping.

Bleeding and use of blood products after heart operations in infants.

Recent studies have suggested that postoperative bleeding is decreased in pediatric heart operations if fresh whole blood instead of blood component therapy is used for postoperative transfusions. Because this is in contrast to our practice to use whole blood for only the priming of the cardiopulmonary bypass circuit and then to use blood components for additional transfusion requirements, it was our interest to analyze the bleeding complications and the use of blood products after heart operations in infants. The patient records of the 73 infants operated on in 1992 were reviewed. The chest tube drainage varied from 3 to 51 ml/kg per 6 hours (mean 10 ml/kg) and it did not correlate with any of the tested clinical or laboratory parameters. One infant underwent reoperation because of surgical bleeding. Disseminated intravascular coagulation developed in another patient. Sixty-eight patients (93%) needed red blood cell supplementation. Sixty-eight percent of patients between 1 month and 1 year old could be treated without any other postoperative transfusion except for red blood cell supplementation. In contrast, in the neonates, platelet concentrates or fresh frozen plasma, or both, were used in 61% of the patients. In addition to the known immaturity of the hemostatic system, the increased need for platelet concentrates in the neonates was attributed to longer cardiopulmonary bypass time, deeper hypothermia in association with circulatory arrest, larger dosages of heparin, and more extensive plasma dilution during cardiopulmonary bypass. In conclusion, a low rate of bleeding complications and acceptably low general blood loss can be achieved postoperatively with blood component therapy.