Outcome of drowned hypothermic children with cardiac arrest treated with cardiopulmonary bypass.

BACKGROUND: There is a lack of data on the outcome of cardiopulmonary bypass (CPB) rewarming of hypothermic children with cardiac arrest following drowning. AIM OF THE STUDY: To retrospectively analyze single-center outcome of drowning victims treated with CPB. MATERIALS AND METHODS: This retrospective study included all hypothermic drowning victims admitted to the Hospital for Children and Adolescents with attempted resuscitation on CPB between 1994 and 2008 inclusive. Median sternotomy and cannulation of the ascending aorta and the right atrium for CPB were performed on all victims. RESULTS: Nine hypothermic drowning victims, comprising five boys and four girls, with a median age of 3.8 years (range, 1.5-10 years). The median submersion time was 38 min (range, 5-75 min) and the median water temperature was 6.5 °C (range, 0.2-16.5 °C). The median core temperature was 21.9 °C (range 17.7-32.8 °C) at arrival to the hospital. All nine children were able to be weaned from CPB. Only one child, with mild to moderate neurological deficit, became a long-term survivor. She was slowly rewarmed up to 33 °C with CPB and kept in mild hypothermia for 48 h. CONCLUSIONS: Large numbers of submerged children can be primarily resuscitated with CPB. Unfortunately, many of them will decease from severe hypoxic brain injury. Slow rewarming with CPB may improve the likelihood of a better neurological outcome.

The CD4(+)CD8(+) and CD4(+) subsets of FOXP3(+) thymocytes differ in their response to growth factor deprivation or stimulation.

The timing of thymic regulatory T (Treg) cell commitment remains unclear. Specifically, there is disagreement as to whether the CD4(+)CD8(+) FOXP3(+) thymocytes are precursors of mature CD4(+) FOXP3(+) Treg cells, or an independent Treg cell lineage. We reasoned that precursors should be more susceptible to apoptosis than mature Treg cells, and tested this by growth factor removal and anti-CD3 stimulation. Both treatments resulted in an increase of CD4(+) FOXP3(+) thymocytes, whereas the frequency of CD4(+)CD8(+) FOXP3(+) thymocytes decreased significantly. These changes were accompanied by an increase of annexin(+) apoptotic cells. Both of these FOXP3(+) subsets expressed higher levels of Bcl-2 and BIM than other thymocytes, and while in our setting expression of BIM seemed to predispose the cells to apoptosis, Bcl-2 had no apparent protective effect. These results indicate that CD4(+)CD8(+) FOXP3(+) thymocytes are more susceptible to apoptosis than mature CD4(+) FOXP3(+) Treg cells. This is consistent with the view that they are still immature and thus likely to represent a precursor population.

Scoliosis after solid organ transplantation in children and adolescents.

The occurrence of scoliosis in children after solid organ transplantation is not known. A total of 196 children, which is 93% of patients surviving kidney, liver and heart transplantation in our country, participated in a cross-sectional survey. All children were screened for rib hump, and those with clinically significant hump (over 6 degrees ) underwent radiographs of the spine. The occurrence of scoliosis was compared to data obtained from a previously published comparison group. Forty-three (21.9%) of the patients had scoliosis greater than 10 degrees , and 21 (10.7%) of them had curves greater than 20 degrees . The RR (95% CI) for scoliosis needing treatment (over 20 degrees ) was 17.0 (6.75-42.7) in the patients as compared with control population. The occurrence of scoliosis was 17.9% of the kidney, 13.6% of the liver and 51.7% of the heart transplant patients (p < 0.001). In a logistic regression model, heart transplantation (OR (95% CI) 7.27 (2.62-20.2)) and growth hormone treatment (3.98 (1.77-8.94)) were most significant risk factors for scoliosis. The risk of scoliosis is increased in patients with solid organ transplantation. Pediatricians treating these patients should be aware of this increased risk to diagnose early curves and to refer these patients to an orthopedic surgeon.

Normal mitral and aortic valve areas assessed by three- and two-dimensional echocardiography in 168 children and young adults.

Our purpose was to investigate the effects of body size on the sizes of mitral (MV) and aortic valve (AV) areas by three-dimensional (3-D) and two-dimensional (2-D) echocardiography and to create the normal values for 3-D echocardiography. A total of 168 healthy subjects aged 2-27 years were studied by digitized 3-DE, 2-DE, and Doppler echocardiography.3-D echocardiography was performed by using rotational acquisition of planes at 18 degrees intervals from a parasternal view with electrocardiogram gating and without respiratory gating. The annular levels of MV and AV were identified from short-axis cut planes and their areas were measured by planimetry. The diameters of mitral annulus, left ventricular outflow tract (LVOT), and aortic annulus were measured by 2-DE from the apical and parasternal long-axis views. Flow indices were measured by Doppler from MV inflow and the flow in LVOT and in the ascending aorta. Both MV and AV annular areas increased linearly in relation to body size. In the total study group the estimated areas for MV were 5.2 +/- 0.9 cm2/m2 by 3-DE, 3.7 +/- 0.5 cm2/m2 by 2-DE, and 2.0 +/- 0.4 cm2/m2 by continuity equation. The respective values for AV were 2.7 +/- 0.5, 2.1 +/- 0.3, and 1.8 +/- 0.4 cm2/m2. MV velocity time integral (VTI)/ascending aorta VTI increased from 0.80 (0.26) to 0.95 (0.23) with increased body surface area (BSA), whereas MV VTI/LVOT VTI was 1.2 (0.2) in all BSA groups. MV and AV annulus areas increase linearly in relation to body size. 3-DE gives greater estimates for the areas than 2-DE and Doppler equation methods. The data obtained from 168 healthy subjects may serve as a reference for clinical use in patients with various cardiac abnormalities.

Left atrial and left ventricular function in healthy children and young adults assessed by three dimensional echocardiography.

OBJECTIVE: To establish normal values of left atrial and left ventricular volumes and function in children and young adults using three dimensional echocardiography (3DE). METHODS: 169 healthy subjects aged 2 to 27 years were studied by digitised 3DE. 3DE was achieved using rotational acquisition of planes at 18 degrees intervals from the parasternal view for the left atrium and from the transthoracic apical view for the left ventricle with ECG gating and without respiratory gating. Left atrial and left ventricular volumes could be calculated throughout the heart cycle, and the respective time-volume curves were reconstructed in each subject. RESULTS: For the analysis the subjects were divided into five groups according to body surface area: 0.5-0.75 m2, 0.75-1.0 m2, 1.0-1.25 m2, 1.25-1.5 m2, and over 1.5 m2. Mean (SD) left atrial maximum volume/body surface area was 19.6 (3.5), 21.7 (3.7), 22.0 (4.7), 24.5 (4.8), and 27.4 (6.4) ml/m2; left ventricular maximum volume/body surface area was 50.1 (8.8), 54.9 (10.1), 56.4 (9.9), 58.7 (11.0), and 64.4 (10.3) ml/m2. Left atrial active emptying increased from 19% to 35% with age (r = 0.34, p < 0.001) and with decreasing heart rate (r = -0.28, p < 0.001). CONCLUSIONS: Transthoracic 3DE is well suited for studying the phasic changes in left atrial and left ventricular volumes in young children as well as in adults. The data obtained from 169 healthy subjects will serve as a reference for further studies in patients with various cardiac abnormalities.

Late results of pediatric cardiac surgery in Finland: a population-based study with 96% follow-up.

BACKGROUND: This population-based study characterizes the history and progress of pediatric cardiac surgery in Finland. For the first time, all defects and procedures are included in an outcome study, reflecting the true effectiveness of operative treatment. METHODS AND RESULTS: All data relating to the operations were collected retrospectively from hospital records. Current patient status was obtained from the population registry. Survival was evaluated with the Kaplan-Meier method applied to all patients and separately to subgroups of patients with the most common defects. The survival rates were compared with those of an age- and sex-matched general population. During the 37 years (1953 to 1989), 6461 patients underwent surgery; 96% of them were traced. The number of operations and the constellation of defects treated increased dramatically over time. Actuarial survival for the 45 years ended October 28, 1998 (the ending date of this study) was 78% for patients versus 93% for the general population. Survival and the number of operations per patient varied widely with the defect. The survival of patients with a surgically closed atrial septal defect was comparable to that of the general population, and such patients rarely needed a reoperation, whereas only 15% of patients with univentricular heart survived for 34 years, and almost all needed at least 2 operations. CONCLUSIONS: The overall survival of patients with cardiac defects corrected surgically in childhood is good compared with their estimated natural course. The increasing number of surgically treatable defects and the growing number of operations per patient reflect the increasing ability to treat more difficult cases.

Perioperative determinants and outcome of cardiopulmonary arrest in children after heart surgery.

OBJECTIVES: To identify perioperative factors associated with postoperative cardiopulmonary arrest (CA) in the pediatric intensive care unit (PICU) in children undergoing cardiovascular surgery, and to report the outcome of cardiopulmonary resuscitation (CPR) in these patients. METHODS: We reviewed the medical records of all patients under 16 years of age who had undergone cardiovascular surgery and sustained CA in PICU in an urban, tertiary care children's hospital over a 5-year period. We used two control groups of patients who recovered without CA. (1) Sixty-five patients, who were operated under deep hypothermic circulatory arrest (DHCA) during the study period. (2) All patients who underwent repair of congenital heart lesions without DHCA in 1994 (n=278). RESULTS: Eighty-two children experienced CA during postoperative care in PICU, mainly from cardiovascular causes. Thirty-four (41%) were declared dead without attempted resuscitation, CPR was initiated in 48 (59%). The primary survival rate was 56% and 1 year survival rate was 19%. The incidence of CA was 3.6% for closed heart operations, 4.9% for intra-cardiac surgery without DHCA, and 27% for operations involving DHCA. Thirty-three per cent of patients with CA arrested during the first 24 postoperative h. Preoperative mechanical ventilation (P=0.03), prostaglandin E1 (P=0.001) and inotropic support (P=0.04) were given significantly more frequently to patients who postoperatively required CPR, compared to control groups. Patients in whom CPR was attempted were younger than the 1994 controls (0.4 vs. 1.2 years; P<0.04), had longer mean aortic-cross-clamp times (76 vs. 51 min; P<0.0001) and cardiopulmonary bypass times (124 vs. 85 min; P<0.0002), and required more inotropic support upon leaving the operating room (P<0.0001). Patients who received CPR had significantly longer DHCA times (53 vs. 32 min; P<0.0002) and required more inotropic support than patients in the DHCA control group (P<0.002). CONCLUSIONS: CA after pediatric cardiac surgery is associated with repair of complex congenital heart anomalies in patients who require preoperative mechanical ventilation and vasoactive agents, prolonged aortic cross-clamp, circulatory arrest; and heavy postoperative inotropic support.

Postoperative nitric oxide therapy in children with congenital heart disease. Can the need be predicted?

The necessity for postoperative inhaled nitric oxide (NO) therapy and predictive factors for that need were retrospectively analysed in 457 paediatric patients at risk of pulmonary hypertensive events following open-heart surgery for congenital heart disease. Inhaled NO was given postoperatively to 46% of the study group and to 23% of all patients undergoing open-heart surgery during the study period. Factors associated with increased need for postoperative NO were age <1 year, Down's syndrome, preoperative pulmonary hypertension and increased pulmonary vascular resistance. Using a multivariate model based on these factors, 73% of the patients who were given NO were identified. Thus, in a setting with unrestricted access to NO therapy, almost half of the patients with cardiac lesions that commonly give rise to postoperative pulmonary hypertension were given postoperative NO. Seventy-three percent of postoperative NO treatment was associated with a relatively small number of pre- and perioperative patient-related risk factors.

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.

Amrinone versus dopamine and nitroglycerin in neonates after arterial switch operation for transposition of the great arteries.

OBJECTIVE: To compare the efficacy and safety of amrinone and a combination of dopamine and nitroglycerin in neonates after reconstructive surgery for transposition of the great arteries. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Thirty-five neonates with transposition of the great arteries. INTERVENTIONS: A loading dose of amrinone, 2 mg/kg, followed by a maintenance infusion of 7.5 microg/kg/min, were administered to 16 neonates before separation from cardiopulmonary bypass. The remaining 19 patients were administered a combination of dopamine, 5 microg/kg/min, and nitroglycerin, 1 microg/kg/min. An open-label epinephrine infusion was administered in both groups as required. 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 (1.7+/-0.5 L/min/m2 [mean +/- SD]) compared with the dopamine-nitroglycerin group (1.4+/-0.4 L/min/m2; p < 0.04). The systemic vascular resistance in the amrinone group was lower (26+/-8 Wood units x m2) than in the dopamine-nitroglycerin group (35+/-12 Wood units x m2; p < 0.02). The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.34+/-0.08) compared with the amrinone group (0.28+/-0.06; p < 0.02). Lower platelet counts were observed in the amrinone group, but no difference in hemorrhagic complications was seen between the groups. CONCLUSION: With the dosage regimen used, supplemented with epinephrine, amrinone provides a higher cardiac output and more favorable oxygen dynamics than a combination of dopamine and nitroglycerin.

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.

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.

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.

Central venous thrombosis after cardiac operations in children.

To evaluate the incidence, mortality, late outcome, and cause of central venous thrombosis after pediatric heart operations and other operations performed with cardiopulmonary bypass, we identified patients with postoperative central venous thrombosis during a 10-year period at a single pediatric hospital. There had been 1591 open heart (with bypass) and 1086 closed heart (no bypass) procedures and 13 operations with cardiopulmonary bypass for extracardiac indications. There were 20 patients with central venous thrombosis, yielding incidences of 1.1% and 0.2% after cardiopulmonary bypass and after closed heart operations, respectively. When neonates were compared with older children (1 to 119 months of age) undergoing heart procedures, a tenfold increase (5.8% vs 0.6%) (p < 0.001) in the incidence of central venous thrombosis was observed. The mortality was eight of 20 (40%). Central venous thrombosis contributed to seven deaths and it was a direct cause of one death. Ten patients were reinvestigated 5 to 108 months after central venous thrombosis. The outcome of surgery was excellent in eight. Two had residual thrombosis, but this was not hemodynamically significant to the cardiorespiratory condition of the patients. During or preceding thrombosis, low levels of antithrombin III and/or protein C and high levels of the plasminogen activator inhibitor were observed in five of the patients. A congenital thrombotic risk factor, "resistance to activated protein C," was found in two of 12 tested patients with central venous thrombosis (17%). In conclusion, central venous thrombosis, especially in neonates, is an important cause of morbidity and mortality after cardiac operations. The cause is multifactorial, with contributions from multiple acquired thrombophilic coagulation abnormalities, and resistance to activated protein C may act as a risk factor for thrombosis already during neonatal period.

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.

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.

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.