Monitoring unfractionated heparin in pediatric patients with congenital heart disease having cardiac catheterization or cardiac surgery.

Determine the effect of age and congenital heart disease (CHD) on whole blood tests for monitoring unfractionated heparin (UFH) in children. Determine correlation with anti-Xa levels in children undergoing cardiac catheterization or cardiac surgery. A prospective cross-sectional study of 211 healthy children about to have minor surgery (median age 3.5 years) and 110 CHD patients (median age 2.1 years) undergoing cardiac catheterization or cardiac surgery. Commonly used whole blood tests (two activated clotting times and an activated partial thromboplastin time; ACT+, ACT-LR, and APTT, respectively) were obtained before procedures and after UFH in CHD patients. Data were analyzed for effect of age and CHD and correlation with anti-Xa levels. In healthy subjects the ACT+ was lower in younger (<3 years) patients while the ACT-LR and APTT were unaffected. CHD patients exhibited an opposite trend with higher values in the younger patients. After bolus heparin the ACT+ exhibited the strongest correlation (r = 0.89) with anti-Xa levels in both locations (the APTT was too sensitive at post-bolus levels). When anti-Xa levels were below 1.0 IU/ml (range of thromboembolism therapy 0.35-0.7 IU/ml), the APTT correlation coefficient was 0.72. Some whole blood coagulation tests are affected by age in healthy children similar to laboratory tests and are variably influenced by the presence of CHD. ACT+ is the most reliable predictor of anti-Xa levels in both catheterization and surgery for pediatric patients. The APTT exhibited stronger correlation with anti-Xa than previous reports of laboratory APTT and warrants further evaluation for monitoring heparin thromboembolism therapy.

Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome.

OBJECTIVES: The purposes of this study are to describe the quality of life and cognitive function in school-aged children who have undergone staged palliation for hypoplastic left heart syndrome (HLHS), and to identify factors that are predictive of neurodevelopmental outcome in this population. METHODS: School-aged survivors with HLHS who had undergone palliative surgery at our institution were identified and mailed a questionnaire to assess subjectively quality of life, school performance, and incidence of medical complications. A subgroup of local patients underwent standardized testing of cognitive function and neurologic examination. These patients were compared with the larger (remote) group of questionnaire respondents to determine whether results may be generalizable to the entire HLHS population. Potential predictors of neurologic and cognitive outcome were tested for their association with test scores using multivariate regression analysis. RESULTS: Questionnaire results were obtained from 115 of 138 eligible children (83%; mean age: 9.0 +/- 2.0 years). Standardized testing was performed in 28 of 34 (82%) eligible local patients (mean age: 8.6 +/- 2.1 years). The majority of parents or guardians described their child's health as good (34%) or excellent (45%) and their academic performance as average (42%) or above average (42%). One third of the children, however, were receiving some form of special education. Chronic medication usage was common (64%); the incidence of medical complications was comparable to that previously reported in children with Fontan physiology. Cognitive testing of the local group demonstrated a median full scale IQ of 86 (range: 50-116). Mental retardation (IQ: <70) was noted in 18% of patients. In multivariate analysis, only the occurrence of preoperative seizures predicted lower full scale IQ. CONCLUSIONS: Although the majority of school-aged children with HLHS had IQ scores within the normal range, mean performance for this historical cohort of survivors was lower than that in the general population.

Management of bleeding and coagulopathy after heart surgery.

Mechanisms of bleeding common to virtually all patients after heart surgery are platelet dysfunction, enhanced fibrinolysis, dilution of all components of the coagulation system, and the presence of heparin and protamine. The use of warfarin is increasing in patients with heart disease requiring surgery. The replenishment of vitamin K-dependent factors beyond a normal prothrombin time is not assessable, and the dilution associated with cardiopulmonary bypass can reach coagulopathic levels. Optimal preoperative preparation is required and intraoperative therapy initiated when indicated. Individualized heparin and protamine dosing, antifibrinolytic drug administration, minimization of blood loss and dilution, and minimal time on cardiopulmonary bypass are basic adjuncts to meticulous surgical hemostasis. When bleeding is observed in the postoperative period, a sequential assessment of the probable cause leads to initial therapy while laboratory test results are obtained. Ongoing assessment for hemodynamic instability caused by accumulated mediastinal blood is needed while managing the bleeding patient. A chest radiograph and transesophageal echocardiogram can be useful in diagnosing cardiac tamponade.

Safety issues in heparin and protamine administration for extracorporeal circulation.

This article reviews past approaches to heparin and protamine dosing and summarizes current practice. The author elucidates his experience with the Celite activated coagulation time (ACT), with attention to his adoption of a value of 400 seconds for this time; the adoption of an ACT of 480 seconds by Bull et al (J Thorac Cardiovasc Surg 69:674-684, 1975) and Young et al (Ann Thorac Surg 26:231-240, 1978); the proposed use of heparin response curves by Bull et al; the author's experience with a unitized dosing system to individualize dosing of heparin; and the use for this purpose by Despotis et al (J Thorac Cardiovasc Surg 110:46-54, 1995) of a system based on protamine titration. In more than 270 adult cardiac surgery patients, the unitized dosing system identified patients with high sensitivity or resistance to heparin and facilitated exact individualized doses to be given to produce the desired effect. Thus, less heparin was used in short bypass runs. Patients received less protamine than they would have with any other formula, and there was less blood loss and fewer transfusions required. Currently, no claims for efficacy or safety can be made for maintaining heparin concentrations greater than 3 U/mL. Pending further clarification, heparin dosage cannot be safely reduced when using heparin-bonded circuits. Aprotinin is not a procoagulant during cardiopulmonary bypass. Emerging studies suggest that graft patency is not affected by aprotinin use. The Celite ACT should not be used to monitor heparin effect and safety when using aprotinin; the kaolin ACT should be used instead.

Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial.

CONTEXT: Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy. OBJECTIVE: To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. DESIGN AND SETTING: A block randomized double-blind clinical trial lasting 20 months at a single academic medical center. PATIENTS: A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia. INTERVENTIONS: Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients. MAIN OUTCOME MEASURES: Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. RESULTS: The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks. CONCLUSIONS: Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.

Lidocaine inhibits blood coagulation: implications for epidural blood patch.

Lidocaine in the epidural space, through inhibitory effects upon coagulation, may contribute to inefficacy of epidural autologous blood patch (EBP). This study was undertaken to evaluate the effect of achievable epidural concentrations of lidocaine on blood coagulation as a step in testing this hypothesis. Ex vivo blood coagulation using whole blood (n = 20) was studied with computerized thrombelastography (TEG). Each blood specimen was exposed to serial dilutions of lidocaine hydrochloride or saline to form end-concentrations of 0.0 mM, 2.3 mM, 4.6 mM, 9.2 mM, 18.5 mM, and 36.9 mM lidocaine. Statistical analysis using analysis of variance for repeated measures revealed that the three highest lidocaine concentrations tested caused hypocoagulable and/or fibrinolytic changes as compared with controls. Achievable epidural admixtures of lidocaine and whole blood will impair coagulation. Therefore, residual lidocaine in the epidural space may contribute to failures of immediate or early EBP.

Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations.

Individual aspects of heparin or protamine dosing have been better controlled than previously as useful tests have become available. Although many variables including drug potency, drug source, and individual patient response have been separately identified, there has not been an attempt to integrate them into a single management strategy. This study was undertaken to learn whether more precise control of drug variables and patient response would affect blood loss and transfusion requirements. Adult patients having primary cardiac operations were prospectively randomized into two groups. A control group received heparin and protamine by conventional methods. The test group received heparin and protamine according to in vitro predictive tests integrating drugs, tests, and patient response. Supplemental protamine was given in this group only if heparin was specifically found by testing. Anticoagulation in all patients was maintained at an activated coagulation time greater than 400 seconds, and any other treatment for bleeding was at the discretion of the clinical team caring for the patients. Testing and treatment for both groups followed routine practice after patient arrival in the intensive care unit. Test patients received slightly more heparin and a markedly lower dose of protamine than the control patients. Testing identified patients with decreased heparin sensitivity (preoperative heparin therapy) and correctly predicted the effective heparin dose. Supplemental protamine was given twice as often to control patients and frequently when no heparin was detectable (retrospectively). Test patients exhibited less 24-hour chest tube drainage (671 ml versus 1298 ml) and fewer patients received transfusion (9/22 versus 18/24) with fewer donor exposures (22/22 versus 101/24). The management strategy used for heparin and protamine added accuracy and precision, which was associated with improved hemostasis. Although the observation is valid, the mechanism or mechanisms are not completely clear. Nevertheless, it is reasonable to apply basic pharmacologic principles and establishment of consistent, predictable protocols that are beneficial. It is against this background that the efficacy of additional drugs or equipment should be assessed. It is quite possible that only marginal if any improvement in hemostasis may be found in patients having primary, uncomplicated cardiac operation with the addition of more costly drugs or equipment.

The metabolic effects of surface cooling neonates prior to cardiac surgery.

Neonates undergoing cardiac surgery at The Children's Hospital of Philadelphia frequently developed metabolic acidemia as they passively cooled prior to the start of cardiopulmonary bypass. This study was performed in an attempt to identify the mechanism for this acidemia. After receiving an initial dose of fentanyl (10 micrograms/kg) and pancuronium, 22 neonates were randomly assigned to maintain normothermia by active warming (Group I), or to permit passive cooling (Group II) before surgery. Arterial blood samples were obtained prior to, and at 10 and 45 min after entering the operating room for the analysis of pH, gas tensions, lactate, pyruvate, plasma free fatty acids, acetoacetate, beta-hydroxybutyrate, total CO2, and glucose concentrations. In the last 11 patients studied, the observation period was extended to 75 min at which time another arterial blood sample was obtained. There was a steady decrease in heart rate as the Group II patients cooled; however, arterial blood pressure did not change in either group. There were no changes in blood values measured in Group I neonates. In the Group II patients, there was a progressive decline in calculated base excess, total CO2, and an increase in serum lactate as the patients cooled. The metabolic acidemia that develops in neonates represents lactate accumulation as a consequence of surface cooling prior to surgery and the institution of cardiopulmonary bypass. Whether lactate accumulates as a result of anaerobic metabolism in underperfused tissue beds or reduced hepatic clearance could not be distinguished in this study. Since neither clinically significant hemodynamic changes nor differences in outcome were found between the two groups, the authors believe this mild lactic acidemia is inconsequential and does not require therapy.

Desmopressin does not decrease bleeding after cardiac operation in young children.

Young children undergoing complex cardiac operation lose more blood after cardiopulmonary bypass than do older patients. This study was designed to investigate the effect of desmopressin on blood loss during the first 24 hours after cardiac operation in children undergoing principally complex surgical procedures. The study consisted of a randomized, blinded comparison of 112 pediatric patients who received either desmopressin 0.3 microgram/kg or saline solution placebo after cardiopulmonary bypass. A coagulation profile including bleeding time, quantitation of von Willebrand factor, and qualitative analysis of the factor VII:von Willebrand factor complex was performed before, 30 minutes after, and 3 hours after the operation. Blood loss and blood replacement were recorded for the first 24 hours after the operation. The surgeon classified the technical difficulty of each procedure as simple or complex. Statistical analysis was performed with Student's unpaired t test and chi 2 analysis. Significance was defined as p < 0.05. Results are listed as mean +/- standard deviation. Data collection was completed for 95 patients. The mean age of all patients was 26 +/- 40 months, and the mean weight was 10 +/- 11 kg, with 84% undergoing complex procedures. There were no differences between the desmopressin and placebo groups with respect to age, weight, or surgical complexity. Twenty-four-hour blood loss and replacement between the desmopressin and placebo groups were not different (blood loss: desmopressin 30 +/- 33 ml/kg, placebo 35 +/- 36; blood replacement: desmopressin 65 +/- 43 ml/kg, placebo 64 +/- 46 ml/kg). Coagulation profiles between the desmopressin and placebo groups were not different at any time. We conclude that desmopressin does not reduce blood loss or blood replacement in young children after cardiopulmonary bypass for either simple or complex cardiac surgical procedures.

Influence of sensor site location on pulse oximetry kinetics in children.

A pulse oximeter sensor is used to monitor changes in arterial hemoglobin oxygen saturation (SpO2) in anesthetized pediatric patients. The authors compared the kinetics of desaturation and resaturation measured by sensors placed over central (tongue, cheek) and peripheral (finger, toe) vascular beds in children with congenital heart disease. Desaturation time was defined as the time which elapsed between the onset of apnea and a 4% decrease in SpO2 from baseline. The desaturation times averaged 24 +/- 12 s, 56 +/- 34 s, and 58 +/- 28 s for the cheek, finger, and toe, respectively (n = 40; P < 0.0001 for cheek versus finger or toe). Resaturation time was defined as the interval between the resumption of ventilation and a 4% increase in SpO2 above the nadir. Resaturation times averaged 12 +/- 8 s for the cheek, 40 +/- 36 s for the finger, and 47 +/- 25 s for the toe (n = 40; P < 0.0001 for cheek versus finger or toe). A comparison of the kinetics at two central sensor sites, cheek and tongue, respectively, revealed no significant differences in desaturation times (20 +/- 10 s vs 21 +/- 9 s) or resaturation times (10 +/- 6 s vs 7 +/- 3 s) (n = 13). The authors conclude that both desaturation and resaturation are detected earlier by centrally placed sensors.

Carbon dioxide prevents pulmonary overcirculation in hypoplastic left heart syndrome.

Circulatory and metabolic homeostasis in patients with hypoplastic left heart syndrome is dependent on a delicate balance between systemic and pulmonary blood flow. Hypocarbia can result in a marked decrease in pulmonary vascular resistance accompanied by pulmonary overcirculation, systemic hypotension, metabolic acidosis, and death. This report illustrates that early and precise control of the arterial carbon dioxide tension using inspired carbon dioxide can be effective in preventing or treating instability arising during management of a patient with hypoplastic left heart syndrome.

The effect of administering or withholding dextrose in pre-bypass intravenous fluids on intraoperative blood glucose concentrations in infants undergoing hypothermic circulatory arrest.

Thirty-six fasted infants under 1 year of age who were scheduled for elective cardiac surgery using hypothermic bypass with circulatory arrest were randomized to receive a lactated Ringer's (LR) solution (group I) or a LR with 5% dextrose solution (group II) in the pre-bypass period. Marked increases in blood glucose concentrations were found following institution of bypass and circulatory arrest in the children in both groups. There was no correlation between the amount of dextrose infused in the pre-bypass period and the presence of hyperglycemia following institution of bypass. A single patient in group I was hypoglycemic (blood glucose less than 30 mg/dL) on the initial glucose determination and the blood glucose did not increase during the pre-bypass period. Elimination of dextrose from the parenteral fluids given before bypass will not eliminate hyperglycemia following institution of bypass; however, it may expose pediatric patients to the risks of hypoglycemia before bypass.