Age-related changes in serum levels of insulin-like growth factor-II and its binding proteins correlate with calcaneal bone mineral density among post-menopausal South-Indian women.

BACKGROUND: Insulin-like growth factor (IGF) system components are important regulators of bone metabolism, which have a predominant role in determining bone mineral density (BMD). While the serum levels of IGF-I are regulated by various systemic hormones and growth factors, IGF-II levels reflect the skeletal production relative to physical activity, mechanical loading, aging, race etc. Though various studies have been carried out among women of different ethnic groups to understand the relationship between serum levels of IGF-II and BMD, the results seem to be quite inconclusive. METHODS: We evaluated the same, recruiting South-Indian women who engage themselves in a wide variety of physical activities pertaining to their profession and life style. RESULTS: Serum levels of IGF-II and IGF binding protein (IGFBP)-3 showed positive correlation with calcaneal BMD, whereas IGFBP-4 showed negative correlation. These IGF system components exhibited similar correlations with serum bone formation markers and opposite trend with bone resorption marker. While both IGF-II and IGFBP-3 levels were observed to be decreased with aging and menopause, IGFBP-4 levels increased. CONCLUSIONS: The alterations in serum levels of IGF-II and its binding proteins due to aging and menopause could be some of the major contributors of decreased calcaneal BMD observed among elderly women.

Unexpected cardiac arrest among children during surgery, a North American registry to elucidate the incidence and causes of anesthesia related cardiac arrest.

Relatively rare adverse events, such as unexpected cardiac arrest, are difficult to study in the clinical setting. These events are often unpredictable in their occurrence (prompting interest in their investigation) and do not occur with sufficient frequency in any single institution to provide an adequate sample for analysis. A disease-specific registry is an epidemiological technique that can be used to collect data on a set of relatively rare unpredictable events. This approach was adopted for investigation of cardiac arrest in children when it became apparent from analysis of malpractice claims that a significant clinical problem existed. This report provides a brief historical account of the development of the Pediatric Peri-Operative Cardiac Arrest (POCA) Registry and elaborates on the methodology including strengths, weaknesses, and practical implementation issues.

Impact of inspired gas mixtures on preoperative infants with hypoplastic left heart syndrome during controlled ventilation.

BACKGROUND: Management strategies for preoperative infants with hypoplastic left heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased inspired carbon dioxide (hypercarbia). There are no studies directly comparing these 2 therapies in humans. This study compares the impact of hypoxia versus hypercarbia on oxygen delivery, under conditions of fixed minute ventilation. METHODS AND RESULTS: Ten anesthetized and paralyzed preoperative infants with HLHS were evaluated in a prospective, randomized, crossover trial comparing hypoxia (17% FIO(2)) with hypercarbia (2.7% FICO(2)). Each patient was treated in a random order (10 minutes per condition) with a recovery period (15 to 20 minutes) in room air. Arterial (SaO(2)) and superior vena caval (SvO(2)) co-oximetry and cerebral oxygen saturation (ScO(2)) measurements were made at the end of each condition and recovery period. ScO(2) was measured by near infrared spectroscopy. Hypoxia significantly decreased both SaO(2) (-5.2+/-1.1%, P=0.0014) and SvO(2) (-5.6+/-1.7%, P=0.009) compared with baseline, but arteriovenous oxygen saturation (AVO(2)) difference (SaO(2)-SvO(2)) and ScO(2) remained unchanged. Hypercarbia decreased SaO(2) (-2.6+/-0.6%, P=0.002) compared with baseline but increased both ScO(2) (9.6+/-1.8%, P=0.0001) and SvO(2) (6+/-2.2%, P=0.022) and narrowed the AVO(2) difference (-8.5+/-2.3%, P=0.005). Both hypoxia and hypercarbia decreased the balance between pulmonary and systemic blood flow (Qp:Qs) compared with baseline. CONCLUSIONS: In preoperative infants with HLHS, under conditions of anesthesia and paralysis, although Qp:Qs falls in both conditions, oxygen delivery is unchanged during hypoxia and increased during hypercarbia. These data cannot differentiate cerebral from systemic oxygen delivery.

Anesthesia-related cardiac arrest in children: initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry.

BACKGROUND: The Pediatric Perioperative Cardiac Arrest (POCA) Registry was formed in 1994 in an attempt to determine the clinical factors and outcomes associated with cardiac arrest in anesthetized children. METHODS: Institutions that provide anesthesia for children are voluntarily enrolled in the POCA Registry. A representative from each institution provides annual institutional demographic information and submits anonymously a standardized data form for each cardiac arrest (defined as the need for chest compressions or as death) in anesthetized children 18 yr of age or younger. Causes and factors associated with cardiac arrest are analyzed. RESULTS: In the first 4 yr of the POCA Registry, 63 institutions enrolled and submitted 289 cases of cardiac arrest. Of these, 150 arrests were judged to be related to anesthesia. Cardiac arrest related to anesthesia had an incidence of 1.4 +/- 0.45 (mean +/- SD) per 10,000 instances of anesthesia and a mortality rate of 26%. Medication-related (37%) and cardiovascular (32%) causes of cardiac arrest were most common, together accounting for 69% of all arrests. Cardiovascular depression from halothane, alone or in combination with other drugs, was responsible for two thirds of all medication-related arrests. Thirty-three percent of the patients were American Society of Anesthesiologists physical status 1-2; in this group, 64% of arrests were medication-related, compared with 23% in American Society of Anesthesiologists physical status 3-5 patients (P < 0.01). Infants younger than 1 yr of age accounted for 55% of all anesthesia-related arrests. Multivariate analysis demonstrated two predictors of mortality: American Society of Anesthesiologists physical status 3-5 (odds ratio, 12.99; 95% confidence interval, 2.9-57.7), and emergency status (odds ratio, 3. 88; 95% confidence interval, 1.6-9.6). CONCLUSIONS: Anesthesia-related cardiac arrest occurred most often in patients younger than 1 yr of age and in patients with severe underlying disease. Patients in the latter group, as well as patients having emergency surgery, were most likely to have a fatal outcome. The identification of medication-related problems as the most frequent cause of anesthesia-related cardiac arrest has important implications for preventive strategies.

Pulmonary function after modified venovenous ultrafiltration in infants: a prospective, randomized trial.

OBJECTIVE: We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants. METHODS: We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded. RESULTS: Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 +/- 1.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.7 mL/cm H(2)O, P =.03) and static (pre-ultrafiltration 2.1 +/- 0.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.1 mL/cm H(2)O, P =.04) compliance. However, there was no significant difference in the change in dynamic (P =.3) or static (P =.7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 +/- 91 hours vs 90 +/- 58 hours) or the length of intensive care unit stay (10.0 +/- 9.1 days vs 7.4 +/- 5.7 days). CONCLUSIONS: Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay.

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.

Efficacy of epsilon-aminocaproic acid in children undergoing cardiac surgery.

OBJECTIVE: To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic epsilon-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 < 0.05). There was no difference between groups in blood products transfused (in milliliters per kilogram or allogenic exposure per patient). Thromboelastography values (maximum amplitude [MA], whole blood clot lysis index at 30 minutes after MA) during CPB were better preserved in the EACA group. 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.

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.

Fibrinolysis in pediatric patients undergoing cardiopulmonary bypass.

OBJECTIVE: Thromboelastographic evaluation of the influence of fibrinolysis on blood loss and blood product transfusions in children during cardiac surgery. DESIGN: Prospective study. SETTING: University-affiliated, pediatric medical center. PARTICIPANTS: Two hundred seventy-eight consecutive children undergoing cardiac surgery. INTERVENTIONS: Blood sampling for coagulation tests, including native and protamine-modified thromboelastography. MEASUREMENTS AND MAIN RESULTS: Blood coagulation tests were measured before, during, and after cardiopulmonary bypass (CPB). Demographic data, perioperative blood loss, and blood product transfusions were prospectively recorded. Fibrinolysis was defined as thromboelastography of A30/MA less than 0.85 (MA, maximum amplitude; A30, amplitude 30 minutes after MA) and was noted in 3% of children pre-CPB, 16% during CPB, and 3% post-CPB. Fibrinolysis before CPB was associated with poor cardiac output. Fibrinolysis during CPB occurred in young children (aged 350 +/- 836 days) undergoing complex surgery with prolonged CPB (119 +/- 48.8 minutes) and deep hypothermia (25.6 degrees C +/- 4.7 degrees C). These patients received blood products after CPB and were not fibrinolytic after transfusion. They incurred similar blood loss (in mL/kg) and received similar volumes of blood products (mL/kg) as age-matched and surgery-matched patients without fibrinolysis. CONCLUSION: A group of children at risk for fibrinolysis during CPB was identified. However, fibrinolysis during CPB did not influence blood loss or the total volume of blood products transfused.

Teaching successful central venous cannulation in infants and children: audio Doppler versus anatomic landmarks.

OBJECTIVE: To determine if vein localization with an audio Doppler increases successful central venous cannulation and decreases complications in infants and children when performed by inexperienced operators, compared with vein localization by anatomic landmarks (ALs). DESIGN: A prospective cohort of infants and children undergoing central venous cannulation for cardiac surgery. SETTING: A university-affiliated children's hospital with a pediatric anesthesia fellowship program. PARTICIPANTS: All infants and children undergoing cardiac surgery between July 1, 1996, and January 1, 1997. INTERVENTIONS: Subjects had central venous catheters (CVCs) placed by an anesthesia fellow by either ALs or audio-Doppler localization of the veins. MEASUREMENTS AND MAIN RESULTS: Eighty-four children were studied. Internal jugular vein (IJV) cannulation was attempted in 71 (85%) children and femoral vein cannulation in 13 (15%) children. Time to catheter insertion, number of needle passes, and artery puncture were noted. Sixty-one of 63 (97%) children had successful central venous cannulation by an anesthesia fellow using audio-Doppler vein localization. This was significantly greater than the 13 of 21 (62%) successful cannulations among children who had veins localized by ALs. Time to insertion did not differ by method of vein localization; however, the number of needle passes was significantly greater in the AL group. Artery puncture did not differ significantly by method of vein localization. CONCLUSION: Vein localization by audio Doppler significantly increases the rate of successful central venous cannulation and decreases the number of needle passes in pediatric patients when used by inexperienced operators.

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.

Endothelial and leukocyte adhesion molecules in inflammation and disease.

Injury associated with ischemia and reperfusion is a significant factor in a number of clinical diseases. We have completed a number of preclinical studies investigating the blockade of leukocyte adhesion molecules in ischemia-reperfusion injury. In our work and in the work of other investigators, monoclonal antibodies directed to CD18, P-selectin and L-selectin were effective in reducing ischemia-reperfusion injury to the rabbit ear and in reducing injury following hemorrhagic shock in both rabbits and nonhuman primates. Ischemia-reperfusion injury was also reduced by synthetic oligosaccharide sLe(x). These studies suggest that adhesion blockade might be effective in the clinical setting.

Postdural puncture headache in pediatric oncology patients.

This prospective cohort study determined the incidence and risk factors for development of postdural puncture headache (PDPH) in children after lumbar puncture (LP). Eighty-six children were enrolled. LPs were performed with use of 22-gauge spinal needles with the bevel oriented parallel to the long axis of the spine. Follow-up telephone interviews and patients' diary of symptoms were collected. Headache brought on by sitting up and relieved by lying down was defined as PDPH. Of the 80 who completed the study, six (8%) developed PDPH. Two (3%) were less than 6 years old and four (5%) were 6 to 12 years of age. Children with a history of headache following a previous LP were nine times as likely to experience PDPH. PDPH occurs not infrequently in children. A prior history of headache is a predisposing factor.

Efficacy of peripherally inserted central venous catheters placed in noncentral veins.

BACKGROUND: Peripherally inserted central venous catheters (PICCs) are commonly used intravenous access devices in children. Although PICCs are intended to be placed in central veins, many fail to reach this location. These noncentral PICCs are used for administration of medications and isotonic solutions. OBJECTIVES: To examine the efficacy of noncentral PICCs for completion of therapy, the complications associated with their use, and the effectiveness of noncentral PICCs as compared with PICCs placed in a central vein. DESIGN: A prospective cohort study of children in whom PICCs were inserted, from January 1, 1994, to January 1, 1996. SETTING: A university-affiliated teaching institution. MAIN OUTCOME MEASUREMENT: Completion of intravenous therapy. RESULTS: A total of 587 PICCs were studied. Thirty-nine percent of PICCs were placed in noncentral veins. Centrally placed PICCs had significantly longer catheter duration compared with those placed noncentrally (16.6 vs 11.4 days, respectively). However, central and noncentral PICCs had similar therapy completion rates (73% and 69%, respectively). Catheter failure because of occlusion and accidental dislodgment were similar for central and noncentral PICCs. Likewise, complications caused by exit-site infection, phlebitis, and catheter-associated sepsis were also similar for catheters in the 2 locations. Catheter survival curves were similar for central and noncentral PICCs. CONCLUSIONS: Our study demonstrates that PICCs placed in noncentral veins provide reliable and safe intravenous access for administration of many medications and isotonic solutions for about 2 weeks' duration. The placement of PICCs in central veins may be restricted to those children who need central vascular access because of the type of intended therapy.

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

UNLABELLED: We investigated the pharmacokinetics and side effects of milrinone in infants and children (< or = 13 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-microg/kg boluses with a final infusion rate of 0.5 microg kg(-1) x min(-1); those in the large dose group (n = 8) received a 50-microg/kg bolus and a 25-microg/kg bolus with a final infusion rate of 0.75 microg x kg(-1) x 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 (Vbeta) 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 x kg(-1) x min(-1)). Thrombocytopenia (defined as platelet count < or = 100,000 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 I.V. 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.