Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion

ObjectiveThe risk for thrombosis is increased after the Fontan operation. It is unknown whether children with univentricular heart disease have an intrinsic coagulation anomaly or acquire a defect in coagulation during the course of the staged repair. This prospective, longitudinal study evaluated changes in coagulation profiles in a cohort of patients with hypoplastic left heart syndrome from stage I palliation through completion of the Fontan operation.MethodsThirty-seven patients with hypoplastic left heart syndrome were enrolled prospectively, and the concentration of factors II, V, VII, VIII, IX, X, proteins C and S, fibrinogen, antithrombin, serum albumin, and liver enzymes were measured before stage I palliation (mean age 4 ± 2 days), before bidirectional Glenn (mean age 5.9 ± 1.8 months), before the Fontan procedure (mean age 27.1 ± 6.6 months), and after the Fontan procedure (mean age 49 ± 17.6months). Healthy children were used as age-matched controls for coagulation factors. Demographic, hemodynamic variables, and elapsed time after the Fontan procedure were evaluated as possible predictors of coagulation abnormalities.ResultsSignificantly lower levels of both procoagulation and anticoagulation factors were demonstrated through to completion of the Fontan procedure. After the Fontan procedure, there was a significantly higher factor VIII level (P < .005) but no correlation with hemodynamic variables or liver function.ConclusionThis longitudinal study in patients with identical cardiac disease and staged surgical procedures confirms the increase in factor VIII level after the Fontan procedure. This is an acquired defect, and although the cause remains to be determined, monitoring factor VIII levels after the Fontan operation could indicate a subset of patients at risk for thrombosis

Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion

ObjectiveThe risk for thrombosis is increased after the Fontan operation. It is unknown whether children with univentricular heart disease have an intrinsic coagulation anomaly or acquire a defect in coagulation during the course of the staged repair. This prospective, longitudinal study evaluated changes in coagulation profiles in a cohort of patients with hypoplastic left heart syndrome from stage I palliation through completion of the Fontan operation.MethodsThirty-seven patients with hypoplastic left heart syndrome were enrolled prospectively, and the concentration of factors II, V, VII, VIII, IX, X, proteins C and S, fibrinogen, antithrombin, serum albumin, and liver enzymes were measured before stage I palliation (mean age 4 ± 2 days), before bidirectional Glenn (mean age 5.9 ± 1.8 months), before the Fontan procedure (mean age 27.1 ± 6.6 months), and after the Fontan procedure (mean age 49 ± 17.6months). Healthy children were used as age-matched controls for coagulation factors. Demographic, hemodynamic variables, and elapsed time after the Fontan procedure were evaluated as possible predictors of coagulation abnormalities.ResultsSignificantly lower levels of both procoagulation and anticoagulation factors were demonstrated through to completion of the Fontan procedure. After the Fontan procedure, there was a significantly higher factor VIII level (P < .005) but no correlation with hemodynamic variables or liver function.ConclusionThis longitudinal study in patients with identical cardiac disease and staged surgical procedures confirms the increase in factor VIII level after the Fontan procedure. This is an acquired defect, and although the cause remains to be determined, monitoring factor VIII levels after the Fontan operation could indicate a subset of patients at risk for thrombosis

Higher hematocrit improves cerebral outcome after deep hypothermic circulatory arrest

AbstractBackground: Various degrees of hemodilution are currently in clinical use during deep hypothermic circulatory arrest to counteract deleterious rheologic effects linked with brain injury by previous reports. Material and methods: Seventeen piglets were randomly assigned to three groups. Group I piglets (n = 7) received colloid and crystalloid prime (hematocrit < 10%), group II piglets (n = 5) received blood and crystalloid prime (hematocrit 20%), group III piglets (n = 5) received blood prime (hematocrit 30%). All groups underwent 60 minutes of deep hypothermic circulatory arrest at 15º C. with continuous magnetic resonance spectroscopy and near-infrared spectroscopy Neurologic recovery was evaluated for 4 days (neurologic deficit score 0, normal, to 500, brain death; overall performance category 1, normal, to 5, brain death). Neurohistologic score (0, normal, to 5+, necrosis) was assessed after the animals were euthanized on day 4. Results: Group I had significant loss of phosphocreatine and intracellular acidosis during early cooling (phosphocreatine in group I, 86.3% ± 26.8%; group II, 117.3% ± 8.6%; group III, 110.9% ± 2.68%; p = 0.0008; intracellular pH in group I, 6.95 ± 0.18; group II, 7.28 ± 0.04; group III, 7.49 ± 0.04; p = 0.0048). Final recovery was the same for all groups. Cytochrome aa3 was more reduced in group I during deep hypothermic circulatory arrest than in either of the other groups (group I, -43.6 ± 2.6; group II, -16.0 ± 5.2; group III, 1.3 ± 3.1; p < 0.0001). Neurologic deficit score was best preserved in group III (p < 0.05 group II vs group III) on the first postoperative day, although this difference diminished with time and all animals were neurologically normal after 4 days. Histologic assessment was worst among group I in neocortex area (group I, 1.33 ± 0.3; group II, 0.22 ± 0.1; group III, 0.40 ± 0.2, p < 0.05, group I vs group II; p = 0.0287, group I vs group III). Conclusion: Extreme hemodilution during cardiopulmonary bypass may cause inadequate oxygen delivery during early cooling. The higher hematocrit with a blood prime is associated with improved cerebral recovery after deep hypothermic circulatory arrest. (J Thorac Cardiovasc Surg 1996;112:1610-21

Extracorporeal membrane oxygenation support after the Fontan operation

ObjectiveExtracorporeal membrane oxygenation has been used to support children with cardiac failure after the Fontan operation. Mortality is high, and causes of mortality remain unclear. We evaluated the in-hospital mortality and factors associated with mortality in these patients.MethodsExtracorporeal Life Support Organization registry data on patients requiring extracorporeal membrane oxygenation after the Fontan operation from 1987 to 2009 were retrospectively analyzed. Demographics and extracorporeal membrane oxygenation data were compared for survivors and nonsurvivors. A multivariable logistic regression model was used to identify factors associated with mortality.ResultsOf 230 patients, 81 (35%) survived to hospital discharge. Cardiopulmonary resuscitation was more frequent (34% vs 17%, P = .04), and median fraction of inspired oxygen concentration was higher (1 [confidence interval, 0.9–1.0] vs 0.9 [confidence interval, 0.8–1.0], P = .03) before extracorporeal membrane oxygenation in nonsurvivors compared with survivors. Extracorporeal membrane oxygenation duration and incidence of complications, including surgical bleeding, neurologic injury, renal failure, inotrope use on extracorporeal membrane oxygenation, and bloodstream infection, were higher in nonsurvivors compared with survivors (P < .05 for all). In a multivariable model, neurologic injury (odds ratio, 5.18; 95% confidence interval, 1.97–13.61), surgical bleeding (odds ratio, 2.36; 95% confidence interval, 1.22–4.56), and renal failure (odds ratio, 2.81; 95% confidence interval, 1.41–5.59) increased mortality. Extracorporeal membrane oxygenation duration of more than 65 hours to 119 hours (odds ratio, 0.33; 95% confidence interval, 0.14–0.76) was associated with decreased mortality.ConclusionsCardiac failure requiring extracorporeal membrane oxygenation after the Fontan operation is associated with high mortality. Complications during extracorporeal membrane oxygenation support increase mortality odds. Prompt correction of surgical bleeding when possible may improve survival

A novel sialyl lewis x analog attenuates cerebral injury after deep hypothermic circulatory arrest

AbstractBackground: The initial step in the inflammatory process, which can be initiated by cardiopulmonary bypass and by ischemia/reperfusion, is mediated by interactions between selectins on endothelial cells and on neutrophils. We studied the effects of selectin blockade using a novel Sialyl Lewis X analog (CY-1503) on recovery after deep hypothermic circulatory arrest in a piglet model. Methods: Twelve Yorkshire piglets were subjected to cardiopulmonary bypass, 30 minutes of cooling, 100 minutes of circulatory arrest at 15°C, and 40 minutes of rewarming. Five animals received a bolus of 60 mg/kg of CY-1503 and an infusion (3 mg/kg per hour) for 24 hours from reperfusion (group O), and 7 randomly selected control piglets received saline solution (group C). Body weight and total body water content were evaluated 3 hours and 24 hours after reperfusion by a bio-impedance technique. Neurologic recovery of animals was evaluated daily by neurologic deficit score (0 = normal, 500 = brain death) and overall performance categories (1 = normal, 5 = brain death). The brain was fixed in situ on the fourth postoperative day and examined by histologic score (0 = normal, 5+ = necrosis) in a blinded fashion. Results: Two of 7 animals in group C died. The neurologic deficit score was significantly lower in group O than in group C (postoperative day 1, P < .001; postoperative day 2, P = .02). The overall performance category was significantly lower in group O than in group C on postoperative day 2 (P = .01). Percentage total body water after cardiopulmonary bypass was significantly higher in group C than in group O (P = .03). Histologic score tended to be higher in group C than in group O, but this difference did not reach statistical significance (group O = 0.5 ± 0.7; group C = 1.3 ± 1.9). Conclusion: Blockade of selectin adhesion molecules by saturation with a Sialyl Lewisxanalog accelerates recovery after 100 minutes of deep hypothermic circulatory arrest in a piglet survival model. (J Thorac Cardiovasc Surg 1999; 117:1204-11

Interaction of temperature with hematocrit level and pH determines safe duration of hypothermic circulatory arrest

AbstractObjectivePrevious studies have demonstrated that both hematocrit level and pH influence the protection afforded by deep hypothermic circulatory arrest. The current study examines how temperature modulates the effect of hematocrit level and pH in determining a safe duration of circulatory arrest. The study also builds on previous work investigating the utility of near-infrared spectroscopy as a real-time monitor of cerebral protection during circulatory arrest.MethodsSeventy-six piglets (9.3 ± 1.2 kg) underwent circulatory arrest under varying conditions with continuous monitoring by means of near-infrared spectroscopy (hematocrit level of 20% or 30%; pH-stat or alpha-stat strategy; temperature of 15°C or 25°C; arrest time of 60, 80, or 100 minutes). Neurologic recovery was evaluated daily by a veterinarian, and the brain was fixed in situ on postoperative day 4 to be examined on the basis of histologic score in a blinded fashion.ResultsMultivariable analysis of total histologic score revealed that higher temperature, lower hematocrit level, more alkaline pH, and longer hypothermic circulatory arrest duration were predictive of more severe damage to the brain (P < .01). Regression modeling revealed that higher temperature exacerbated the disadvantage of a lower hematocrit level and longer arrest times but not pH strategy. Normalized oxyhemoglobin nadir time, derived from near-infrared spectroscopy, was positively correlated with neurologic recovery on the fourth postoperative day and with total histologic injury score (P < .0001).ConclusionHematocrit level and pH, as well as temperature, determine the safe duration of hypothermic circulatory arrest. Near-infrared spectroscopy is a useful real-time monitor of safe duration of circulatory arrest

Use of rapid-deployment extracorporeal membrane oxygenation for the resuscitation of pediatric patients with heart disease after cardiac arrest

AbstractIntroduction: We have recently used extracorporeal membrane oxygenation as a means of rapidly resuscitating pediatric patients with heart disease after cardiopulmonary arrest, in whom conventional resuscitation measures have failed. Methods: We developed a fully portable extracorporeal membrane oxygenation circuit that is maintained vacuum and carbon dioxide–primed at all times. When needed, the circuit is crystalloid-primed and can be ready for use within 15 minutes. Since February 1996, we have used this rapid-deployment circuit to resuscitate 11 pediatric patients in full cardiopulmonary arrest. Results: The median age of the 11 patients was 120 days (2 days to 4.6 years). Nine patients had a cardiac arrest after cardiac surgery. One patient had a cardiac arrest during cardiac catheterization and one patient had a cardiac arrest before cardiac surgery. Median duration of cardiopulmonary resuscitation was 55 minutes (range 20 to 103 minutes), with no difference in the duration of cardiopulmonary resuscitation between survivors and nonsurvivors. Ten of 11 patients (91%) were weaned from extracorporeal membrane oxygenation and seven (64%) survived to hospital discharge. Six patients are long-term survivors, five of whom are in New York Heart Association class I; one survivor is in class II. Seven patients resuscitated with extracorporeal membrane oxygenation before the use of this rapid-deployment circuit had a median duration of cardiopulmonary resuscitation of 90 minutes, with two (28.6%) survivors. Conclusions: The use of rapid-deployment extracorporeal membrane oxygenation results in shorter resuscitation times and improved survival in pediatric patients with heart disease after cardiopulmonary arrest. (J Thorac Cardiovasc Surg 1998;116:305-11

Survival and Clinical Course at Fontan After Stage One Palliation With Either a Modified Blalock-Taussig Shunt or a Right Ventricle to Pulmonary Artery Conduit

ObjectivesWe sought to determine whether the type of shunt used at stage one palliation (S1P) affected the survival and the perioperative course through Fontan completion.BackgroundAlthough improved surgical and interstage survival have been demonstrated with the use of the right ventricle to pulmonary artery (RV-PA) conduit compared with a modified Blalock-Taussig shunt (BTS) at S1P, it is unknown whether this effect will be observed in long-term follow-up.MethodsAll patients who underwent a S1P during 2002 and 2003 (n = 80) at our institution were included for analysis. Patients were followed until death or June 1, 2007. Perioperative variables at Fontan completion were recorded.ResultsFor the entire cohort, cumulative survival for those who underwent a RV-PA conduit (n = 34) was 79.4% at 3 years compared with 65.8% in the modified BTS group (n = 46) (log-rank = 0.31). At Fontan (n = 44), when compared with those who had received a modified BTS, those who had a RV-PA conduit placed at S1P had no difference in the median duration of ventilation (21 h [range 10 to 96 h] vs. 26.5 h [range 7 to 204 h], p = 0.09) or hospital stay (9 days [range 5 to 29 days] vs. 10 days [range 6 to 48 days], p = 0.89), although length of stay in the intensive care unit was shorter (2 days [range 0 to 6 days] vs. 4 days [range 1 to 25 days], p = 0.01). Sixty-seven percent of the RV-PA conduit group had at least one PA intervention 3 years after S1P compared with 42.8% in the modified BTS group (log-rank = 0.11).ConclusionsNonstatistically significant trends toward improved cumulative survival and increased PA interventions were demonstrated in patients who had a RV-PA conduit placed at S1P. Longitudinal follow-up of larger groups of randomized patients is required to determine the influence of the RV-PA conduit on long-term outcomes

Design and Rationale of Safe Pediatric Euglycemia After Cardiac Surgery (SPECS): A Randomized Controlled Trial of Tight Glycemic Control After Pediatric Cardiac Surgery

Objectives: To describe the design of a clinical trial testing the hypothesis that children randomized to tight glycemic control with intensive insulin therapy after cardiac surgery will have improved clinical outcomes compared to children randomized to conventional blood glucose management. Design: Two-center, randomized controlled trial. Setting: Cardiac ICUs at two large academic pediatric centers. Patients: Children from birth to those aged 36 months recovering in the cardiac ICU after surgery with cardiopulmonary bypass. Interventions: Subjects in the tight glycemic control (intervention) group receive an intravenous insulin infusion titrated to achieve normoglycemia (target blood glucose range of 80–110 mg/dL; 4.4–6.1 mmol/L). The intervention begins at admission to the cardiac ICU from the operating room and terminates when the patient is ready for discharge from the ICU. Continuous glucose monitoring is performed during insulin infusion to minimize the risks of hypoglycemia. The standard care group has no target blood glucose range. Measurements and Main Results: The primary outcome is the development of any nosocomial infection (bloodstream, urinary tract, and surgical site infection or nosocomial pneumonia). Secondary outcomes include mortality, measures of cardiorespiratory function and recovery, laboratory indices of nutritional balance, immunologic, endocrinologic, and neurologic function, cardiac ICU and hospital length of stay, and neurodevelopmental outcome at 1 and 3 yrs of age. A total of 980 subjects will be enrolled (490 in each treatment arm) for sufficient power to show a 50% reduction in the prevalence of the primary outcome. Conclusions: Pediatric cardiac surgery patients may recognize great benefit from tight glycemic control in the postoperative period, particularly with regard to reduction of nosocomial infections. The Safe Pediatric Euglycemia after Cardiac Surgery trial is designed to provide an unbiased answer to the question of whether this therapy is indeed beneficial and to define the associated risks of therapy