Glyn D. Williams

The effects of dexmedetomidine on cardiac electrophysiology in children.

BACKGROUND:Dexmedetomidine (DEX) is an &agr;2-adrenergic agonist that is approved by the Food and Drug Administration for short-term (<24 h) sedation in adults. It is not approved for use in children. Nevertheless, the use of DEX for sedation and anesthesia in infants and children appears to be increasing. There are some concerns regarding the hemodynamic effects of the drug, including bradycardia, hypertension, and hypotension. No data regarding the effects of DEX on the cardiac conduction system are available. We therefore aimed to characterize the effects of DEX on cardiac conduction in pediatric patients. METHODS:Twelve children between the ages of 5 and 17 yr undergoing electrophysiology study and ablation of supraventricular accessory pathways had hemodynamic and cardiac electrophysiologic variables measured before and during administration of DEX (1 &mgr;g/kg IV over 10 min followed by a 10-min continuous infusion of 0.7 &mgr;g · kg−1 · h−1). RESULTS:Heart rate decreased while arterial blood pressure increased significantly after DEX administration. Sinus node function was significantly affected, as evidenced by an increase in sinus cycle length and sinus node recovery time. Atrioventricular nodal function was also depressed, as evidenced by Wenckeback cycle length prolongation and prolongation of PR interval. CONCLUSION:DEX significantly depressed sinus and atrioventricular nodal function in pediatric patients. Heart rate decreased and arterial blood pressure increased during administration of DEX. The use of DEX may not be desirable during electrophysiology study and may be associated with adverse effects in patients at risk for bradycardia or atrioventricular nodal block.

Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open-heart surgery.

UNLABELLED In this prospective cohort study of 548 children undergoing open-heart surgery, we evaluated demographic and perioperative factors to identify variables associated with perioperative blood loss and blood product transfusions. Using multivariate analysis, younger patient age was found to be the variable most significantly associated with bleeding and transfusions. Higher preoperative hematocrit, complex surgery, lower platelet count during cardiopulmonary bypass (CPB), and longer duration of deep hypothermic circulatory arrest were also significantly associated with bleeding and transfusion. Excessive postoperative chest tube (CT) drainage was associated with intraoperative bleeding. Independently associated variables accounted for 76% of the variability in CT output measured after 2 h in intensive care. Patients were subdivided into children aged < or =1 yr (infants) and children >1 yr; infants bled more intraoperatively (P<0.005); had greater cumulative CT output at 2, 6, 12, and 24 h (P<0.0001); and received more blood products (P<0.0001). Factors associated with bleeding and transfusions varied with patient age. Lower body core temperature during CPB was highly associated with blood loss and transfusions in infants, whereas resternotomy, preoperative congestive heart failure, and prolonged duration of CPB were significant factors associated with bleeding and transfusions in children >1 yr old. IMPLICATIONS Knowledge of the factors associated with blood loss and blood product transfusions can help to identify children at risk of excessive bleeding after open-heart surgery.

Anesthetic management of children with pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is associated with significant perioperative risk for major complications, including pulmonary hypertensive crisis and cardiac arrest. Several mechanisms of hemodynamic deterioration, including acute increases in pulmonary vascular resistance (PVR), alterations of ventricular contractility and function and coronary hypoperfusion can contribute to morbidity. Anesthetic drugs exert a variety of effects on PVR, some of which are beneficial and some undesirable. The goals of balanced and cautious anesthetic management are to provide adequate anesthesia and analgesia for the surgical procedure while minimizing increases in PVR and depression of myocardial function. The development of specific pulmonary vasodilators has led to significant advances in medical therapy of PAH that can be incorporated in anesthetic management. It is important that anesthesiologists caring for children with PAH be aware of the increased risk, understand the pathophysiology of PAH, form an appropriate anesthetic management plan and be prepared to treat a pulmonary hypertensive crisis.

Coagulation Tests During Cardiopulmonary Bypass Correlate With Blood Loss in Children Undergoing Cardiac Surgery

OBJECTIVES To examine whether coagulation tests, sampled before and during cardiopulmonary bypass (CPB), are related to blood loss and blood product transfusion requirements, and to determine what test value(s) provide the best sensitivity and specificity for prediction of excessive hemorrhage. DESIGN Prospective. SETTING University-affiliated, pediatric medical center. PARTICIPANTS Four hundred ninety-four children. INTERVENTIONS Coagulation tests. MEASUREMENTS AND MAIN RESULTS Demographic, coagulation test, blood loss, and transfusion data were noted in consecutive children undergoing cardiac surgery. Laboratory tests included hematocrit (Hct), prothrombin time, partial thromboplastin time (PTT), platelet count, fibrinogen concentration, and thromboelastography. Stepwise linear regression analysis indicated that platelet count during CPB was the variable most significantly associated with intraoperative blood loss (in milliliters per kilogram) and 12-hour chest tube output (in milliliters per kilogram). Other independent variables associated with blood loss were thromboelastography maximum amplitude (MA) during CPB, preoperative PTT, preoperative Hct, and preoperative thromboelastography angle and shear modulus values. Thromboelastography MA during CPB was the only variable associated with total products transfused (in milliliters per kilogram). Of all tests studied, platelet count during CPB (< or = 108,000/microL) provided the maximum sensitivity (83%) and specificity (58%) for prediction of excessive blood loss (receiver operating characteristic analysis). Blood loss was inversely related to patient age; neonates received the most donor units (median, 8 units; range, 6 to 10 units). CONCLUSIONS During cardiac surgery, coagulation tests (including thromboelastography) drawn pre-CPB and during CPB are useful to identify children at risk for excessive bleeding. Platelet count during CPB was the variable most significantly associated with blood loss.

Ketamine does not increase pulmonary vascular resistance in children with pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation.

BACKGROUND:The use of ketamine in children with increased pulmonary vascular resistance is controversial. In this prospective, open label study, we evaluated the hemodynamic responses to ketamine in children with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg). METHODS:Children aged 3 mo to 18 yr with pulmonary hypertension, who were scheduled for cardiac catheterization with general anesthesia, were studied. Patients were anesthetized with sevoflurane (1 minimum alveolar anesthetic concentration [MAC]) in air while breathing spontaneously via a facemask. After baseline catheterization measurements, sevoflurane was reduced (0.5 MAC) and ketamine (2 mg/kg IV over 5 min) was administered, followed by a ketamine infusion (10 &mgr;g · kg−1 · min−1). Catheterization measurements were repeated at 5, 10, and 15 min after completion of ketamine load. Data at various time points were compared (ANOVA, P < 0.05). RESULTS:Fifteen patients (age 147, 108 mo; median, interquartile range) were studied. Diagnoses included idiopathic pulmonary arterial hypertension (5), congenital heart disease (9), and diaphragmatic hernia (1). At baseline, median (interquartile range) baseline pulmonary vascular resistance index was 11.3 (8.2) Wood units; 33% of patients had suprasystemic mean pulmonary artery pressures. Heart rate (99, 94 bpm; P = 0.016) and Pao2 (95, 104 mm Hg; P = 007) changed after ketamine administration (baseline, 15 min after ketamine; P value). There were no significant differences in mean systemic arterial blood pressure, mean pulmonary artery pressure, systemic or pulmonary vascular resistance index, cardiac index, arterial pH, or Paco2. CONCLUSIONS:In the presence of sevoflurane, ketamine did not increase pulmonary vascular resistance in spontaneously breathing children with severe pulmonary hypertension.

Pharmacokinetics and side effects of milrinone in infants and children after open heart surgery

We investigated the pharmacokinetics and side effects of milrinone in infants and children (<or=to13 yr) after open heart surgery in this prospective, open-label study. Milrinone binding to cardiopulmonary bypass (CPB) circuitry was also examined in out two groups. Children in the small dose group (n = 11) received two 25-micro g/kg boluses with a final infusion rate of 0.5 micro g [center dot] kg-1 [center dot] min-1; those in the large dose group (n = 8) received a 50-micro g/kg bolus and a 25-micro g/kg bolus with a final infusion rate of 0.75 micro g [center dot] kg-1 [center dot] min-1. Blood samples for milrinone concentration were drawn 30 min after each bolus, at steady state, and after discontinuing the milrinone infusion. Pharmacokinetics were evaluated using traditional and nonlinear mixed effects modeling analysis. Milrinone kinetics best fit a two-compartment model. Steady-state plasma levels in the small and large dose groups were within the adult therapeutic range (113 +/- 39 and 206 +/- 74 ng/mL, respectively). The volumes of distribution (V beta) in infants (0.9 L/kg) and children (0.7 L/kg) were not different, but infants had significantly lower milrinone clearance (3.8 vs 5.9 mL [center dot] kg-1 [center dot] min-1). Thrombocytopenia (defined as platelet count <or=to100,000 mm-3) occurred in 58%, and the risk increased significantly with duration of infusion. Tachyarrythmias were noted in two patients. Milrinone did not bind to CPB circuitry. We conclude that milrinone is cleared more rapidly in children than in adults. The major complication was thrombocytopenia. Implications: Most pediatric dosing is based on data published for adults. Infants and children have kinetics that differ from adults. We studied the distribution of IV milrinone in infants and children after open heart surgery. Milrinone had a larger volume of distribution and a faster clearance in infants and children than in adults, and dosing should be adjusted accordingly. (Anesth Analg 1998;86:283-9)

Association between age and blood loss in children undergoing open heart operations

BACKGROUND Although recent studies indicated young children are at risk for increased perioperative hemorrhage after open heart operations, the associations between patient age, blood loss and blood product transfusions have not been fully defined in children. METHODS Perioperative blood loss and blood product transfusion data were recorded for 414 consecutive children undergoing open heart procedures. The children were in the following age groups: 1 month or younger, group 1; older than 1 month to 12 months, group 2; older than 1 year to 5 years, group 3; and older than 5 years, group 4. RESULTS Postoperative blood loss and blood product transfusions were inversely related to age and differed significantly between the four age groups. Multiple preoperative and intraoperative factors that possibly influence hemostasis also differed significantly between age groups. Median units transfused within 72 hours differed significantly with age (p < 0.0001): group 1, 8 units (range, 1 to 19 units); group 2, 6 units (range, 0 to 21 units); group 3, 2 units (range, 0 to 23 units); and group 4, 0 units (range, 0 to 38 units). CONCLUSIONS Blood loss and transfusions vary inversely with age. Per kilogram of body weight, neonates bled more and received more donor products than any other age group.

Efficacy of ϵ-aminocaproic acid in children undergoing cardiac surgery

Abstract Objective: To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic ϵ-aminocaproic acid (EACA) and a control group matched for age, resternotomy, and surgery in children undergoing cardiac surgery. Design: Nested case-control study. Setting: University-affiliated, pediatric medical center. Participants: Same study period; 70 patients in EACA group and 70 patients in control group. Interventions: Prophylactic EACA administered intravenously (load, 150 mg/kg, infusion; 30 mg/kg/h) to 70 patients at increased risk for bleeding (reoperation or Ross procedure). Measurements and Main Results: Coagulation test values were measured before, during, and after cardiopulmonary bypass (CPB). Intraoperative blood loss, postoperative chest tube output, and allogenic blood product transfusions were recorded. Comparison of demographic and surgical data indicated close matching of the EACA and control groups. The EACA group ((median, 25th to 75th quartile] 15.6 mL/kg; 9.2 to 26.3 mL/kg) had less intraoperative blood loss than the control group (22.2 mL/kg; 14.3 to 36.3 mL/kg; p = 0.02). Postoperative chest tube output at 6 hours (p = 0.08), 12 hours (p = 0.07), and 24 hours (p = 0.08) was not significantly different between groups. Fewer EACA group patients required reexploration for bleeding (p Conclusion: EACA reduced intraoperative blood loss but did not significantly decrease blood product transfusions. Lack of efficacy may be related to relative underdosing and should be further studied.

Brain Monitoring and Protection During Pediatric Cardiac Surgery

With advances in medical care, survival after cardiac surgery for congenital heart disease has dramatically improved, and attention is increasingly focused on longterm functional morbidities, especially neurodevelopmental outcomes, with their profound consequences to patients and society. There are multiple reasons for concern about brain injury. Some cardiac defects are associated with brain anomalies and altered cerebral blood flow regulation. Brain imaging studies have demonstrated that injury to gray and white matter is quite frequent before heart surgery in neonates. Cardiopulmonary bypass and deep hypothermic circulatory arrest are associated with shortand longer-term adverse neurologic outcome. Additional brain injury can occur during the patients recovery from surgery. Strategies to optimize neurologic outcome continue to evolve. With new technological developments, perioperative neurologic monitoring of small children has become easier, and data suggest these modalities usefully identify adverse neurologic events and might predict outcome. Monitoring methods to be discussed include processed electroencephalography, near infrared spectroscopy, and transcranial Doppler ultrasound. Alternative perfusion techniques to deep hypothermic circulatory arrest have been developed, such as regional antegrade cerebral perfusion during cardiopulmonary bypass. Other neuroprotective strategies employed during open-heart surgery include temperature regulation, acid-base management, degree of hemodilution, blood glucose control and anti-inflammatory therapies. Evidence of the impact of these measures on neurologic outcome is examined, and deficiencies in our current understanding of neurologic function in children with congenital heart disease are identified.

Perioperative complications in children with pulmonary hypertension undergoing general anesthesia with ketamine

Background:  Pulmonary arterial hypertension (PAH) is associated with significant perioperative risk for major complications in children, including pulmonary hypertensive crisis and cardiac arrest. Uncertainty remains about the safety of ketamine anesthesia in this patient population.