A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles.

UNLABELLED: Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study's research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after. IMPLICATIONS: The use of ultra-short-acting opioids may be an appropriate technique for infants less than 2 mo old when tracheal extubation after surgery is anticipated.

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis.

UNLABELLED: Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic. IMPLICATIONS: Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures.

UNLABELLED: Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 microg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (< or =2 mo), older infants (> 2 mo to < 2 yr), young children (2 to < 7 yr), older children (7 to < 13 yr), adolescents (13 to < 16 yr), and young adults (16 to < 18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil's effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P < or = 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants < 2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants < 2 mo of age (90 mL. kg(-1). min(-1)) and infants 2 mo to 2 yr (92 mL. kg(-1). min(-1)) than in the other groups (means, 46 to 76 mL. kg(-1). min(-1)). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 microg/kg may cause hypotension in anesthetized children. IMPLICATIONS: The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.

Rapid endotoxin-induced alterations in myocardial calcium handling: obligatory role of cardiac TNF-alpha.

BACKGROUND: Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation of tumor necrosis factor alpha (TNF-alpha) expression in the heart. METHODS: Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-alpha, anti-TNF-alpha antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-alpha concentrations in coronary perfusate and myocardium. RESULTS: Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-alpha accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-alpha antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-alpha mimicked the LPS effects with faster onset. CONCLUSIONS: Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-alpha is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-alpha production, abnormal calcium cycling, and decreased contractility in intact hearts.

Bispectral index monitoring in children undergoing mild hypothermic cardiopulmonary bypass.

BACKGROUND: In this prospective, cohort study of 15 children (median age 7.7 years, range 4.9-16.5 years) undergoing atrial septal defect repair, we evaluated changes in the Bispectral index (BIS) as a potential monitor of level of consciousness during cardiac anaesthesia. METHODS: Identical cardiac surgery, cardiopulmonary bypass (CPB) and anaesthetic techniques were used, including mild hypothermia and an early extubation protocol. BIS, mean arterial pressure, heart rate and tympanic temperature were recorded at baseline postinduction (Tbaseline), skin incision (Tincis), sternotomy (Tsternot), aortic cannulation (Tcann), nadir temperature (Tnadir), rewarmed (Trewarmed), immediate post-CPB (TpostCPB), chest drain insertion (Tdrains), sternal wires (Twire), skin closure (Tclosed) and spontaneous movement (Tmove). As a measure of stress response, serum lactate, glucose, norepinephrine and epinephrine levels were measured at Tbaseline, Tsternot, Tcann, Tnadir, Trewarmed and Tdrains. Explicit memory testing was undertaken prior to hospital discharge. RESULTS: BIS increased significantly during the rewarming phase (Trewarmed versus Tbaseline and Tnadir, P<0.001). Lactate, epinephrine and glucose levels were also significantly elevated at Trewarmed. There were no correlations between BIS and the increase in epinephrine, lactate and glucose during rewarming, nor with changes in heart rate or mean arterial pressure during surgery. All patients had an uneventful recovery without evidence for explicit recall. CONCLUSIONS: The increase in BIS during the rewarming phase could reflect an increase in conscious level, and is consistent with the reported risk for awareness during this phase of cardiac surgery.

Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts.

BACKGROUND: Severe myocardial hypertrophy is associated with decreased tolerance to ischemia compared with normal hearts. We hypothesized that treatment with insulin-like growth factor-1 (IGF-1) improves postischemic myocardial recovery by increasing glucose uptake during ischemia and early reperfusion. METHODS: Banding of the thoracic aorta in 10-day-old rabbits created pressure-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic banded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia with or without IGF-1 in the preischemic perfusate and cardioplegia followed by 30 minutes of reperfusion. RESULTS: 2-Deoxyglucose uptake (31P-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. Insulin-like growth factor-1 restored glucose uptake and PI-3-kinase activity to control levels in the hypertrophied hearts and both effects were blocked by wortmannin (a PI-3-kinase inhibitor). Postischemic developed pressure was significantly improved in IGF-1-treated hearts compared with untreated or IGF-1+wortmannin-treated hypertrophied hearts. CONCLUSIONS: These data indicate that IGF-1 improves glucose uptake and tolerance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are likely mediated through a PI-3-kinase-dependent pathway.

Inhibition of tumor necrosis factor-alpha improves postischemic recovery of hypertrophied hearts.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has been implicated in the pathogenesis of heart failure and ischemia-reperfusion injury. Effects of TNF-alpha are initiated by membrane receptors coupled to sphingomyelinase signaling and include altered metabolism and calcium cycling, contractile dysfunction, and cell death. We postulate that pressure-overload hypertrophy results in increased myocardial TNF-alpha expression and that it contributes to decreased contractility in hypertrophied infant hearts subjected to ischemia-reperfusion. METHODS AND RESULTS: Neonatal rabbits underwent aortic banding to induce LV hypertrophy. Myocardial TNF-alpha protein expression increased progressively with LV hypertrophy. Serum TNF-alpha was detected only after the onset of heart failure. Before onset of ventricular dilatation and heart failure (determined by serial echocardiograms), hearts from aortic banded and age-matched control rabbits were perfused in the Langendorff mode and subjected to 45 minutes of ischemia and 30 minutes of reperfusion. Postischemic recovery was impaired in hypertrophied hearts, but addition of neutralizing anti-rabbit TNF-alpha antibody to cardioplegia and perfusate solutions restored postischemic function. This effect was mimicked by treatment with the ceramidase inhibitor N-oleoyl ethanolamine. TNF-alpha inhibition also was associated with faster postischemic recovery of phosphocreatine, ATP, and pH as assessed by (31)P nuclear magnetic resonance spectroscopy. Intracellular calcium handling, measured by Rhod 2 spectrofluorometry, demonstrated lower diastolic calcium levels and higher systolic calcium transients in anti-TNF-alpha treated hearts. CONCLUSIONS: TNF-alpha is expressed in myocardium during compensated pressure-overload hypertrophy and contributes to postischemic myocardial dysfunction. Inhibition of TNF-alpha signaling significantly improves postischemic contractile function, myocardial energetics, and intracellular calcium handling.

Hemostatic changes in pediatric neurosurgical patients as evaluated by thrombelastograph.

UNLABELLED: Thromboembolic events are a known complication in neurosurgical patients. There is evidence to suggest that a hypercoagulable state may develop perioperatively. Thrombelastograph (TEG) coagulation analysis is a reliable method of evaluating hypercoagulability. We evaluated coagulation by using TEG data in pediatric neurosurgical patients undergoing craniotomy to determine whether a hypercoagulable state develops intraoperatively or postoperatively. Thirty children undergoing craniotomy for removal of a tumor or seizure focus were studied. Blood was analyzed with TEG) data by using native and celite techniques, at three time points for each patient: preoperatively after induction of anesthesia; intraoperatively during closure of the dura; and on the first postoperative day. Compared with preoperative indices, closing and postoperative celite TEG values were indicative of hypercoagulability with shortened coagulation time values (P < 0.001), prolonged alpha angle divergence values (P < 0.001), and above-normal TEG coagulation indices (P < or = 0.002). Reaction time values were shortened, and maximal amplitude of clot strength values were prolonged but did not reach statistical significance. Hypercoagulation develops early after resection of brain tissue in pediatric neurosurgical patients as assessed by using TEG data. Further studies are needed to determine the clinical significance of this hypercoagulable state. IMPLICATIONS: Hypercoagulability in postoperative neurosurgical patients has been demonstrated in the adult population, but few studies have dealt with the pediatric population. We found that children undergoing craniotomy for focal resection, lobectomy, and hemispherectomy are hypercoagulable as detected by thrombelastograph coagulation analysis. Further studies are needed to determine whether this is clinically significant.

Post-ischemic PKC inhibition impairs myocardial calcium handling and increases contractile protein calcium sensitivity.

OBJECTIVE: Protein kinase C (PKC) activation impairs contractility in the normal heart but is protective during myocardial ischemia. We hypothesized that PKC remains activated post-ischemia and modulates myocardial excitation-contraction coupling during early reperfusion. METHODS: Langendorff-perfused rabbit hearts where subjected to 25 min unmodified ischemia and 30 min reperfusion. Total PKC activity was measured, and the intracellular translocation pattern of PKC-alpha, -delta, -epsilon, and -eta assessed by immunohistochemistry and fractionated Western immunoblotting. The PKC-inhibitors chelerythrine and GF109203X were added during reperfusion and also given to non-ischemic hearts. Measurements included left ventricular function, intracellular calcium handling measured by Rhod-2 spectrofluorometry, myofibrillar calcium responsiveness in beating and tetanized hearts, and metabolic parameters. RESULTS: Total PKC activity was increased at end-ischemia and remained elevated after 30 min of reperfusion. The translocation pattern indicated PKC-epsilon as the main active isoform during reperfusion. Post-ischemic PKC inhibition affected mainly diastolic relaxation, with lesser effect on contractility. Both PKC inhibitors increased the Ca(2+) responsiveness of the myofilaments as indicated by a leftward shift of the calcium-to-force relationship and increased maximum calcium activated tetanic pressure. Diastolic Ca(2+) removal was delayed and the post-ischemic [Ca(2+)](i) overload further exacerbated. Depressed systolic function was associated with a lower amplitude of [Ca(2+)](i) transients. CONCLUSION: PKC is activated during ischemia and remains activated during early reperfusion. Inhibition of PKC activity post-ischemia impairs functional recovery, delays diastolic [Ca(2+)](i) removal, and increases Ca(2+) sensitivity of the contractile apparatus, resulting in impaired diastolic relaxation. Thus, post-ischemic PKC activity may serve to restore post-ischemic Ca(2+) homeostasis and attenuate contractile protein calcium sensitivity during the period of post-ischemic [Ca(2+)](i) overload.

Lipopolysaccharide internalization activates endotoxin-dependent signal transduction in cardiomyocytes.

We tested the hypothesis that bacterial lipopolysaccharide (LPS) must be internalized to facilitate endotoxin-dependent signal activation in cardiac myocytes. Fluorescently labeled LPS was used to treat primary cardiomyocyte cultures, perfused heart preparations, and the RAW264.7 macrophage cell line. Using confocal microscopy and spectrofluorometry, we found that LPS was rapidly internalized in cardiomyocyte cultures and Langendorff-perfused hearts. Although LPS uptake was also observed in macrophages, only a fraction of these cells were found to internalize endotoxin to the extent seen in cardiomyocytes. Colocalization experiments with organelle or structure-specific fluorophores showed that LPS was concentrated in the Golgi apparatus, lysosomes, and sarcomeres. Similar intracellular localization was demonstrated in cardiomyocytes by transmission electron microscopy using gold-labeled LPS. The internalization of LPS was dependent on endosomal trafficking, because an inhibitor of microfilament reorganization prevented uptake in both cardiomyocytes and whole hearts. Inhibition of endocytosis specifically restricted early activation of extracellular signal-regulated kinase proteins and nuclear factor-kappaB as well as later tumor necrosis factor-alpha production and inducible nitric oxide synthase expression. In conclusion, we have demonstrated that bacterial endotoxin is internalized and transported to specific intracellular sites in heart cells and that these events are obligatory for activation of LPS-dependent signal transduction.

Stress response in infants undergoing cardiac surgery: a randomized study of fentanyl bolus, fentanyl infusion, and fentanyl-midazolam infusion.

UNLABELLED: There have been significant changes in the management of neonates and infants undergoing cardiac surgery in the past decade. We have evaluated in this prospective, randomized, double-blinded study the effect of large-dose fentanyl anesthesia, with or without midazolam, on stress responses and outcome. Forty-five patients < 6 mo of age received bolus fentanyl (Group 1), fentanyl by continuous infusion (Group 2), or fentanyl-midazolam infusion (Group 3). Epinephrine, norepinephrine, cortisol, adrenocortical hormone, glucose, and lactate were measured after the induction (T1), after sternotomy (T2), 15 min after initiating cardiopulmonary bypass (T3), at the end of surgery (T4), and after 24 h in the intensive care unit (T5). Plasma fentanyl concentrations were obtained at all time points except at T5. Within each group epinephrine, norepinephrine, cortisol, glucose and lactate levels were significantly larger at T4 (P values < 0.01), but there were no differences among groups. Within groups, fentanyl levels were significantly larger in Groups 2 and 3 (P < 0.001) at T4, and among groups, the fentanyl level was larger only at T2 in Group 1 compared with Groups 2 and 3 (P < 0.006). There were no deaths or postoperative complications, and no significant differences in duration of mechanical ventilation or intensive care unit or hospital stay. Fentanyl dosing strategies, with or without midazolam, do not prevent a hormonal or metabolic stress response in infants undergoing cardiac surgery. IMPLICATIONS: We demonstrated a significant endocrine stress response in infants with well compensated congenital cardiac disease undergoing cardiac surgery, but without adverse postoperative outcome. The use of large-dose fentanyl, with or without midazolam, with the intention of providing "stress free" anesthesia, does not appear to be an important determinant of early postoperative outcome.

Ischemic dysfunction in transgenic mice expressing troponin I lacking protein kinase C phosphorylation sites.

To determine the in vivo functional significance of troponin I (TnI) protein kinase C (PKC) phosphorylation sites, we created a transgenic mouse expressing mutant TnI, in which PKC phosphorylation sites at serines-43 and -45 were replaced by alanine. When we used high-perfusate calcium as a PKC activator, developed pressures in transgenic (TG) perfused hearts were similar to wild-type (WT) hearts (P = not significant, NS), though there was a 35% and 32% decrease in peak-systolic intracellular calcium (P < 0.01) and diastolic calcium (P < 0.005), respectively. The calcium transient duration was prolonged in the TG mice also (12-27%, ANOVA, P < 0.01). During global ischemia, TG hearts developed ischemic contracture to a greater extent than WT hearts (41 +/- 18 vs. 69 +/- 10 mmHg, perfusate calcium 3.5 mM, P < 0.01). In conclusion, expression of mutant TnI lacking PKC phosphorylation sites results in a marked alteration in the calcium-pressure relationship, and thus susceptibility to ischemic contracture. The reduced intracellular calcium and prolonged calcium transients suggests that a potent feedback mechanism exists between the myofilament and the processes controlling calcium homeostasis.

Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy.

Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoires, cytokine expression and presence of enterovirus-specific antigens. IDC patients who underwent heart transplantation at different times after the onset of heart failure were studied. A cardiac infiltrate of CD4+ and CD8+ T cells was present together with activated macrophages. Furthermore, the same Vbeta gene families, previously found to be skewed in hearts from fulminant cases of CVB3+-IDC, together with two additional Vbeta gene families, Vbeta1 and 5B, were increased. IL-1beta, IL-2, IL-6 and IFN-gamma were expressed in the myocardium while others, like IL-4 were not. In conclusion, an orchestrated complex of immune mechanisms seems to be the basis of IDC etiopathogenesis.

Surgical outcome of double-outlet right ventricle with subpulmonary VSD.

BACKGROUND: Optimal management of double-outlet right ventricle with subpulmonary ventricular septal defect remains controversial. We reviewed our 7-year experience with patients who had this anatomic configuration. METHODS: Between January 1992 and January 1999, 20 patients underwent an arterial switch operation (ASO group), and 12 underwent a bidirectional Glenn procedure followed by a modified Fontan in 10 (Glenn/Fontan). Mean follow-up was 23 +/- 18 months. RESULTS: An initial palliative operation was done in 19 patients (9 in the ASO group, 10 in the Glenn/Fontan group). There were no deaths in the Glenn/Fontan group. Four patients in the ASO group died within 33 days postoperatively. Two of them had a single coronary artery, 1 had a straddling mitral valve, 1 had a hypoplastic aortic arch, and 1 had multiple ventricular septal defects. Three patients had reoperation for subaortic stenosis (n = 2) or pulmonary stenosis (n = 1) after the ASO. Four patients (3 in the ASO group, 1 in the Glenn/Fontan) required a pacemaker for postoperative complete atrioventricular block. Actuarial survival at 5 years for the entire group was 87% (70% confidence interval, 81% to 93%). CONCLUSIONS: The ASO remains our preferred treatment for infants with double-outlet right ventricle and subpulmonary ventricular septal defect. However, associated anatomic defects are important risk factors.

Improving glucose metabolism and/or sarcoplasmic reticulum Ca2+-ATPase function is warranted for immature pressure overload hypertrophied myocardium.

The cellular mechanisms of abnormal calcium regulation and excitation-contraction coupling in relation to glucose metabolism in the hypertrophied heart are not well understood. The present study evaluated the myocardial mechanics of 6-7-week-old pressure overload hypertrophied rabbit hearts in response to dobutamine by (1) serial echocardiograms in vivo and (2) isolated Langendorff perfusion. Cytosolic Ca2+([Ca2+]i) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression were measured by fluorescence spectroscopy and Western immunoblotting, respectively. The effect of glycolytic inhibition by 2-deoxy-D-glucose +/- pyruvate was also evaluated. Both systolic and diastolic [Ca2+]i tended to be higher and diastolic calcium removal (tauCa) significantly slower in the hypertrophied heart. The myocardial response to dobutamine was blunted and dobutamine insignificantly improved tauCa. The SERCA2 protein level was higher in early hypertrophy, but was significantly reduced by 6 weeks of age, with progressive contractile failure. Inhibition of glycolysis or SERCA2 caused an increase in [Ca2+]i as well as a slower tauCa. Pyruvate completely preserved myocardial function and [Ca2+]i handling during glycolytic inhibition. It was concluded that in this model of advanced pressure overload hypertrophy, contractile failure and inotrope insensitivity are associated with increased [Ca2+]i, slower tauCa and reduced sensitivity of the contractile proteins to Ca2+. These changes occur in association with downregulation of the SERCA2, probably caused by impaired glucose metabolism.

Efficacy of simulated epinephrine-containing epidural test dose after intravenous atropine during isoflurane anesthesia in children.

BACKGROUND AND OBJECTIVES: A double-blind, randomized study was performed to investigate heart rate (HR) and blood pressure responses to 2 doses of intravenous (IV) epinephrine (0.5 and 0.75 microg/kg) in 61 children, ages 3 months to 12 years. METHODS: Anesthesia was maintained with isoflurane (age-adjusted 1 minimal alveolar concentration [MAC]) in oxygen. All patients received IV atropine (10 microg/kg) and 5 minutes later were randomized to receive IV solutions (0.1 mL/kg) containing 1% lidocaine (n = 19, group I) with saline; lidocaine 1% with epinephrine 0.5 microg/kg (n = 21, group II); or lidocaine 1% with epinephrine 0.75 microg/kg (n = 21, group III). HR was recorded at 0, 15, 30, 45, 60, 90 seconds, and 2, 3, 4, and 5 minutes after test-dose injection. Systolic blood pressure (SBP), diastolic blood pressure, and end-tidal carbon dioxide were recorded at steady-state isoflurane anesthesia, after the injection of atropine, and at 45-second intervals after test-dose injections. RESULTS: Median maximum increases in HR were similar in groups II and III at 19 and 22 beats per minute (beats/min), respectively. An HR increase of > or =10 beats/min was observed in 19 of 21 patients who received 0.5 microg/kg epinephrine and 21 of 21 patients receiving 0.75 microg/kg. None of the patients in group I developed HR increases > or =10 beats/min. SBP increased > or =15 mm Hg in 17 of 21 patients in group II and 19 of 21 in group III. No dysrhythmias or T-wave amplitude change was noted. CONCLUSIONS: A simulated epidural test dose containing lidocaine 1 mg/kg with epinephrine 0.75 microg/kg, administered IV following atropine, may reliably increase HR to indicate unintentional injection into epidural vessels of children anesthetized with 1 MAC isoflurane.

Vesnarinone restores contractility and calcium handling in early endotoxemia.

BACKGROUND: Endotoxin (lipopolysaccharide, LPS) is a trigger of the systemic inflammatory response. We have previously found that vesnarinone and amrinone, when given before LPS, prevented cytokine production and LPS-related cardiac dysfunction. We tested the hypothesis that vesnarinone would improve intracellular Ca(2+) handling and calcium-activated contractile force after the onset of endotoxemia. METHODS AND RESULTS: Adult rabbits received a bolus injection of LPS or vehicle. Vesnarinone (3 mg/kg) was given intravenously 90 minutes later. Two hours after LPS administration, hearts were perfused in the isolated Langendorff mode. Peak left ventricular developed pressure, +/-dp/dt, oxygen consumption (MVO(2)), and ratexpressure product were evaluated in conjunction with fluorescent spectroscopic determinations of intracellular calcium concentrations (Ca(i)) and the rate of Ca(i) transient decline during diastole (tauCa). Peak left ventricular developed pressure and +/-dp/dt were significantly lower in the LPS group. These were completely restored by vesnarinone. There was significantly slower diastolic calcium removal (increased tauCa) in LPS hearts that was also corrected by vesnarinone; however, the cytosolic calcium overload characteristic of LPS hearts was only partially improved. Reduced mechanical inefficiency (the ratio of rate-pressure product to MVO(2)) and myofilament sensitivity to Ca(i) were also significantly improved by vesnarinone. CONCLUSIONS: Acute endotoxemia caused contractile protein calcium insensitivity, oxygen wastage, and abnormal calcium cycling. Vesnarinone, given in the rescue mode, normalized LPS-induced myocardial dysfunction and partially restored abnormal calcium cycling. Although the mechanisms responsible for these effects require further clarification, it appears that agents such as vesnarinone may be useful to treat inflammatory-induced myocardial dysfunction.

Pulmonary artery trauma due to balloon dilation: recognition, avoidance and management.

OBJECTIVES: We reviewed the management and outcome of patients experiencing pulmonary artery (PA) trauma during balloon dilation (BD). BACKGROUND: Balloon dilation of the PA is important in the management of peripheral pulmonary stenosis. Successful BD requires a controlled tear of the PA; excessive tearing can produce complications ranging from pseudoaneurysms to rupture and death. The incidence and optimum management for such complications are unreported. METHODS: All records of patients who underwent branch PA dilation between June 1984 and October 1997 were reviewed; those with a significant complication were analyzed. RESULTS: Of 1,286 catheterizations in 782 patients, PA trauma (excluding isolated pulmonary edema and PA aneurysms) was identified in 29 catheterizations in 26 patients. Tears occurred distal to the area of stenosis in most cases (62%). Intensive medical management, with and without catheter directed therapy, was employed. The damaged PA was successfully coil embolized in five patients, four of whom survived; temporary balloon occlusion did not prevent death in two patients. There were six deaths from pulmonary hemorrhage. A case control analysis demonstrated that PA trauma was significantly associated with pulmonary hypertension. CONCLUSIONS: Pulmonary artery trauma associated with BD occurs mostly distal to the site of narrowing, is associated with underlying pulmonary hypertension and is frequently (5/12 or 42%) fatal in those with unconfined tears. Intensive management strategies as well as attention to distal balloon position may reduce incidence and mortality. Coil occlusion of the damaged PA appears to be a valuable strategy to prevent fatal hemorrhage.

Parameters associated with perioperative baffle fenestration closure in the Fontan operation.

OBJECTIVE: To identify clinical parameters indicating perioperative fenestration closure in children who underwent the fenestrated Fontan operation. DESIGN: Retrospective. SETTING: Single children's hospital. PARTICIPANTS: Patients who underwent a fenestrated Fontan operation in 1996 through 1997 (n = 101). INTERVENTION: A fenestrated Fontan operation was performed in children with single-ventricle physiology. MEASUREMENTS AND MAIN RESULTS: Early perioperative closure of the fenestration occurred in 14 patients (group 1), whereas the fenestration remained patent in 87 patients (group 2). The groups were compared by the following parameters: demographics, cardiac catheterization and ultrasound data, and use of aspirin or warfarin preoperatively and intraoperatively by assessing the composition of the cardiopulmonary bypass solution, use of ultrafiltration and antifibrinolytics, protamine dose, last hematocrit on cardiopulmonary bypass, and requirement of blood products. Immediately postoperatively in the intensive care unit (ICU), cardiac filling pressures (central venous and left atrial pressure), coagulation profile, cardiac rhythm, chest tube drainage, length of stay in the ICU, and use of atrial pacing were reviewed. Significant indicators of early fenestration closure in this study as determined by multivariate stepwise logistic regression were a high transpulmonary pressure gradient (p = 0.015) and a higher oxygen saturation (p = 0.001) 1 hour after arrival in the ICU, a low fibrinogen level (p < 0.0001), and the need for temporary atrial pacing (p = 0.029). The fenestration was reopened in 13 patients in group 1. In 101 patients, there was no early mortality, and all patients survived to discharge. CONCLUSION: Factors that correlated with postoperative fenestration closure in the fenestrated Fontan operation in this study were a high transpulmonary pressure gradient and a high oxygen saturation 1 hour after arrival in the ICU, a low fibrinogen level, and the need for temporary atrial pacing.

Intraoperative recurrent laryngeal nerve monitoring during video-assisted throracoscopic surgery for patent ductus arteriosus.

OBJECTIVE: To develop a technique to identify and localize the recurrent laryngeal nerve (RLN) during video-assisted thoracoscopic surgery (VATS) for patent ductus arteriosus. DESIGN: Prospective clinical study. SETTING: Children's hospital. PARTICIPANTS: Sixty infants and children scheduled for elective closure of patent ductus arteriosus. INTERVENTIONS: With parental informed consent, 60 infants and children undergoing elective VATS for patent ductus arteriosus were studied. A thin, pencil-point, Teflon-coated, stimulating probe allowed direct stimulation (<2 mA, 100-msec pulse width) of the left RLN inside the thorax. A commercially available 4-channel neurologic monitor recorded compound evoked electromyograms (EMGs) from the left RLN and right RLN (as control) by needle electrodes placed percutaneously in the neck. Hoarseness, stridor, feeding difficulties, and voice changes were assessed postoperatively. MEASUREMENTS AND MAIN RESULTS: Left RLN EMGs were easily obtained in 59 of the 60 patients. The surgeon correctly identified the RLN visually once in the first 7 patients; this ability subsequently improved. EMG localization of the location or course of the RLN altered dissection, clip size, or clip position in 37 of 59 patients. CONCLUSION: Intraoperative EMG to identify location and route of the RLN was easy to perform, was effective in identifying RLN position, and appeared to facilitate dissection and clipping of the ductus.