Resource use and health outcomes of paediatric extracorporeal membrane oxygenation.

The use of extracorporeal membrane oxygenation can be rationalised by the assumption that non-zero survival after refractory cardiorespiratory failure represents improved outcome. Survivors may have cognitive and or functional morbidities, require complex ongoing care, and as a consequence consume considerable healthcare resources.

ABO-incompatible heart transplantation: a perfusion strategy.

Infants with fatal cardiac disease often die awaiting transplantation because of the shortage of donor hearts. The Hospital for Sick Children (HSC), Toronto, Canada, has researched and applied the concept of crossing the blood group compatibility barrier. Heart transplantation at HSC unrestricted by ABO compatibility greatly contributed to decreasing the mortality rate among infants on the waiting list from 58% to 10%. From January 1996 to January 2002, 16 infants less than 14 months of age received ABO-incompatible heart transplants at our institution. The cardiopulmonary bypass (CPB) circuit is primed with additional volume to replace the patient's blood volume. Packed red blood cells (PRBC) used in priming must be ABO-compatible with the recipient. All plasma components and platelets must contain no anti-A or anti-B antibodies to donor or recipient. CPB is initiated and the patient's venous blood is collected into a transfusion bag and sent to the blood bank. The total amount collected should be one and a half to two times the patient's blood volume. The plasma is separated and discarded, returning only the PRBC, thus reducing the concentration of circulating antibodies to blood group antigens. Our team has experienced an 87% survival rate with this technique. The success is believed to be associated with the recipients' immunologic immaturity. Newborns do not produce isohemagglutinins, and serum anti-A and anti-B antibody titers usually remain low until 12-14 months of age. The complement system is not fully developed, therefore, the mediators of hyperacute rejection are absent during early infancy. Heart transplantation unrestricted by the need for ABO compatibility would effectively expand the available donor pool and decrease waiting times.

Whole blood heparin concentrations do not correlate with plasma antifactor Xa heparin concentrations in pediatric patients undergoing cardiopulmonary bypass.

This study was designed to test the validity of whole blood heparin concentration (WHBC) measurements using an on-site protamine titration assay with the Hepcon instrument (Medtronic Blood Management, Parker, CO, USA) in pediatric patients less than 1 year old undergoing cardiopulmonary bypass (CPB). The validity of the Hepcon measurements was examined via a test of correlation with the gold standard plasma antifactor Xa activity (anti-Xa) assay. Fifty-one patients (23 females and 28 males) under 1 year old (mean age 5.3 months) were studied prospectively. Blood samples were taken at 5 min into CPB and at the end of CPB for the WBHC, plasma anti-Xa activity, and hematocrit (Hct). The WBHC was converted to plasma heparin level using a formula taking into account the collection of blood into citrate solution and the effect of the citrate on the hematocrit. While a nonparametric statistical analysis revealed that the mean corrected values from the Hepcon instrument were not significantly different from the mean anti-Xa values (p = 0.070 at 5 min on CPB, p = 0.518 at the end of CPB), there was no significant correlation between these values at either 5 min into CPB (r = 0.113, p = 0.429) or at the end of CPB (r = -0.247, p = 0.080). The lack of correlation between the two assays may be related to the extreme hemodilution observed during CPB in small children, which leads to very low concentrations of coagulation proteins. Due to this discrepancy, whole blood heparin monitors should be further evaluated in children undergoing CPB.

Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass.

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

Determinants of success in pediatric cardiac patients undergoing extracorporeal membrane oxygenation.

BACKGROUND: The purpose of this retrospective study is to determine the possible predictors of successful cardiac recovery using extracorporeal membrane oxygenation (ECMO) and the practical limits of ECMO support. METHODS: Information was gathered on 31 consecutive children with myocardial failure who could not be resuscitated with other means and underwent ECMO at the Hospital for Sick Children before January 1994. RESULTS: Of the children who underwent ECMO as a means of cardiac rescue, 14/31 (45%) were weaned successfully. Two distinct groups of children were evident based on their initial indications for ECMO: those who had postcardiotomy myocardial dysfunction (n = 25) and those with cardiomyopathy or myocarditis (n = 6). Children with residual defects after cardiotomy (n = 10) did not survive ECMO. Four of the 6 children with cardiomyopathy or myocarditis were weaned successfully. In either group of patients ECMO support beyond 6 days failed to resuscitate the myocardium; all attempts to violate this "time barrier" in our study inevitably failed. CONCLUSIONS: Postcardiotomy residual defects are a contraindication to ECMO. If children with residual defects are excluded, successful weaning from ECMO can be achieved in almost 70%, with almost all recovery occurring with the first 6 days of ECMO.

Heparin therapy during cardiopulmonary bypass in children requires ongoing quality control.

Heparin therapy for children undergoing cardiopulmonary bypass (CPB) is monitored in the operating room by automated whole blood activated clotting times (ACT). For many years our institution used Hemochron (HC) ACT machines but changed to HemoTec (HT) ACT machines because they required a smaller blood sample and provided results in duplicate. When HemoTec ACT machines were introduced at our institution, the surgical team was concerned that increased amounts of heparin were being administered to our patients during CPB. This study was conducted to investigate the potential mechanisms responsible for these clinical observations. First, we compared ACT values on ex vivo blood samples from 20 consecutive pediatric patients (6 samples each) during CPB. The HC ACT values were significantly and systematically increased over HT ACT values (HC: 750 +/- 40 vs HT: 418 +/- 26, Mean +/- SEM, p < 0.01). 94% of all HC ACT values were above 450 s compared to only 27% of HT ACT values. If HT ACT values had been used for patient monitoring, all patients would have received more heparin to achieve ACT values above 450 s. The two machines reported similar ACT values when heparin was added in vitro to whole blood (0.1-5.0 units/ml), (HC: Y = 98X + 104, r2 = 0.93 HT: Y = 82X + 109, r2 = 0.94). Heparin concentrations in our patients following a bolus of 300 U/kg of heparin, but prior to CPB were 3.2 +/- 0.07 units/ml. Following the initiation of CPB, heparin concentrations decreased to 1.3 +/- 0.05, reflecting, in part hemodilution by the pump prime (1 U of heparin/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs.

There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates. While receiving ECMO therapy, the critically ill infant needs various medications. We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction. Two closed ECMO circuits were set up at rates of 320 ml/min. One circuit was new and the other was used clinically for 5 days. Morphine at 8 ng/ml, gentamicin 10 micrograms/ml, vancomycin 40 micrograms/ml, phenobarbital 20 micrograms/ml, and phenytoin 20 micrograms/ml were injected into the circuit at 1-h intervals. Blood samples were drawn from the circuit at 10, 30, 60, and 240 minutes after injection. In the new circuit, drugs were eliminated as follows: vancomycin 36%, gentamicin 10%, phenobarbital 17%, phenytoin 43%, morphine 36%. In the used system, levels fell to a much smaller extent: vancomycin 11%, phenobarbital 6%, gentamicin 0%, phenytoin 0%, and morphine 16%. In a child receiving 20 micrograms/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane. Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is. Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO.

Parenteral administration of 8-methoxypsoralen in photopheresis.

BACKGROUND: Extracorporeal photochemotherapy (EP) is used for the treatment of cutaneous T-cell lymphoma (CTCL), progressive systemic sclerosis (PSS), pemphigus vulgaris, and rheumatoid arthritis. During this procedure, the oral administration of the photoactive drug 8-methoxypsoralen (8-MOP) results in an unpredictable range of serum levels and in side effects limiting its efficacy. OBJECTIVE: To circumvent this limitation, extracorporeally administrable 8-MOP (EX-8-MOP) was developed. It is administered directly to the leukocyte/plasma concentrate in the treatment bag of the EP apparatus before irradiation with UVA light. METHODS: Efficacy, tolerance, and side effects of EX-8-MOP were evaluated in 108 consecutive treatments of 16 patients who had previously been treated with oral 8-MOP (91 treatments). RESULTS: With EX-8-MOP constant drug levels for UV light exposure were obtained; for equivalent levels only a small fraction of the oral dose (1/250 to 1/500) was required with none of the side effects associated with oral 8-MOP. Effective and reproducible inhibition of lymphocyte proliferation and cell viability was attained. No difference in clinical efficacy could be observed. CONCLUSION: EX-8-MOP eliminates the need for premedication and drug level monitoring of 8-MOP and should improve the effectiveness of EP.

Method for measurement of circumduction of the thumb to evaluate results of opponensplasty.

A simple method for measuring circumduction of the thumb, by using a ratio of the range of motion to the length of the first metacarpal, is described. This method can be of value in assessing many aspects of thumb function, especially the improvement in function after opponensplasty. The improved ability to position the thumb in a useful location, both for pinch and grasp, appears to correlate well with the patient's use of the hand for previously impossible tasks.