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We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

We evaluated safety and feasibility of the transvenous limb perfusion gene delivery method in muscular dystrophy. A dose escalation study of single limb perfusion with 0.9% saline starting with 5% of limb volume was carried out in adults with muscular dystrophies under intravenous analgesia/anesthesia. Cardiac, vascular, renal, muscle, and nerve functions were monitored. A tourniquet was placed above the knee with inflated pressure of 310 mm Hg. Infusion was carried out with a clinically approved infuser via an intravenous catheter inserted in the saphenous vein with a goal infusion rate of 80 ml/minute. Infusion volume was escalated stepwise to 20% limb volume in seven subjects. No subject complained of any post procedure pain other than due to needle punctures. Safety warning boundaries were exceeded only for transient depression of limb tissue oximetry and transient elevation of muscle compartment pressures; these were not associated with nerve, muscle, or vascular damage. Muscle magnetic resonant imaging (MRI) demonstrated fluid accumulation in muscles of the perfused lower extremity. High-pressure retrograde transvenous limb perfusion with saline up to 20% of limb volume at above infusion parameters is safe and feasible in adult human muscular dystrophy. This study will serve as a basis for future gene transfer clinical trials.

Although pediatric cardiac critical care, as a distinct field of interest, is a relatively recent development, treating critically ill patients has always been a substantial part of clinical pediatric cardiology. In addition, even pediatric cardiologists who do not provide primary care for

Cardiopulmonary interaction is the term that is used to describe the inseparable connection between the heart and lungs. In health, the cardiovascular and pulmonary systems are in perfect balance. In disease, derangements of either system leads to dysfunction in the other. Physicians attempt to improve health with therapeutic interventions (positive pressure ventilation) typically aimed at treating disease (pneumonia with hypoxia) in one system (lungs) with resultant positive (recruitment of alveoli) and negative (ventilator induced lung injury) consequences and secondary impact on the other system (heart with decreased cardiac output). This manuscript will review the physiologic basis of normal cardiopulmonary interactions and the pathophysiology that occurs in specific disease processes affecting children with congenital cardiac disease. Lastly, we will present current data highlighting therapeutic interventions aimed at improving cardiopulmonary interactions.

The aim of this study was to assess the feasibility of using serial bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage and inflammation in the airways of pediatric patients with acute burn or inhalation injury. This was a prospective, longitudinal, descriptive pilot study conducted at the Burn and Pediatric Intensive Care Units in a tertiary care medical center. Six consecutively intubated and mechanically ventilated pediatric patients with acute inhalational injuries were studied. Serial BALF specimens from clinically indicated bronchoscopies were used to measure DNA and cytokine levels. BALF DNA levels for the six pediatric burn subjects were the highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients and was higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF interleukin-6, interleukin-8, and transforming growth factor-β1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11,917 ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burn or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for the treatment of acute inhalational injuries.

In conclusion, femoral artery obstruction occurs frequently (32%) in infants

Between May 1984 and April 1993, 59 children underwent balloon angioplasty of a native coarctation at our institution. The follow-up protocol included a cardiac catheterization 1 to 2 years after angioplasty, which was performed in 90% of patients withor = 2 years follow-up. Angioplasty caused an acute decrease in peak systolic gradient from 46 +/- 2 to 15 +/- 2 mm Hg, without early aneurysm or emergent surgical intervention in any patient. Based on follow-up data, a satisfactory result was obtained in 38 patients (64%; 70% confidence limit: 58% to 71%), defined as a residual systolic gradient20 mm Hg and no aneurysm. In these patients the gradient decreased acutely from 43 +/- 2 to 9 +/- 1 mm Hg, was 6 +/- 1 mm Hg at follow-up catheterization, and 9 +/- 2 mm Hg by clinical evaluation 4.4 +/- 0.3 years after angioplasty. Twenty-one patients (36%; 70% confidence limit: 29% to 42%) had an unsatisfactory result due to a residual gradientor = 20 mm Hg (n = 19) or aneurysm formation (n = 3), or both. Restenosis occurred in 6 patients, and occurred more in infants than in childrenor = 12 months of age (3 of 5 infants vs 3 of 41 children, p = 0.01). Thus, balloon angioplasty provides an effective initial treatment strategy for native coarctation in most children aged12 months.

Pulse contour cardiac output (PCCO) analysis is a technique for continuous cardiac output (CO) monitoring through an arterial catheter after calibration by transpulmonary thermodilution (TPTD). Studies in adults show good correlation with pulmonary artery thermodilution (PATD) CO. Data are limited in children and patients with hemodynamic instability. The objective was to determine whether TPTD CO and PCCO analysis correlate with PATD CO in a piglet model of severe hemorrhagic shock. Mixed venous oxygen saturation (SVO2) was also compared with PATD CO.Prospective animal study.University animal research laboratory.Domesticated piglets, 24-37 kg.Hemorrhagic shock was created by graded hemorrhage in anesthetized piglets. Hemorrhage was initiated to achieve mean arterial pressure plateaus of 60, 50, 40, 30, and 20 mm Hg.CO was measured by PATD and simultaneously with two femoral artery PCCO catheters. At each mean arterial pressure plateau, one PCCO catheter was recalibrated by TPTD; the other catheter was not recalibrated during hemorrhage. TPTD CO, PCCO measurements from each catheter, and SVO2 were compared with PATD CO at each mean arterial pressure level. TPTD CO and recalibrated PCCO showed excellent correlation (r2 = .96 and .97) and small bias (+0.11 and +0.14 L/min), respectively, compared with PATD. Without recalibration, PCCO measurements were not accurate during rapid hemorrhage (r2 = .22). SVO2 decline did not correlate as well with PATD CO (r2 = .69).TPTD CO and recalibrated PCCO analysis correlate well with PATD CO in this severe hemorrhagic shock model. The mean difference is small (0.15 L/min) and is not clinically significant. With rapid changes in blood pressure or intravascular volume, PCCO is not accurate unless recalibrated by TPTD CO. SVO2 did not correlate well with CO in this model.

To evaluate the efficacy of probiotics in reducing the rates of nosocomial infection in pediatric intensive care.Randomized, double-blind, placebo-controlled trial.A 16-bed pediatric intensive care unit in a university-affiliated children's hospital.Sixty-one pediatric patients were enrolled from April 2004 until December 2004. Screening of all patients admitted occurred on a daily basis. Patients were excluded if they had the following: evidence/suspicion of intestinal perforation, evidence/suspicion of mechanical gastrointestinal obstruction, absolute neutrophil countor =0.5 x 10(9) cells/L, judgment by the attending physician that unable to tolerate the enteral volume necessary for administration, use of a probiotic preparation at any time in the week before study entry, participation in another clinical trial, lack of parental presence, or lack of parental consent.Patients were randomized to receive either one capsule of Lactobacillus rhamnosus strain GG (Culturelle, ConAgra Foods, Omaha, NE) or placebo capsule of insulin once a day until discharge from the hospital.Sixty-one patients were randomized: 31 in the treatment group and 30 on the placebo group. Three patients in the control group developed four infections. Six patients in the treatment group developed 11 infections. The relative risk of developing infection in the treatment group was 1.94 (confidence interval [CI], 0.53 to 7.04; p = .31). The mean number of infections in the treatment and control groups was 1.83 and 1.33, respectively, with a difference of 0.5 (p = .52). No serious adverse effects in the study population were noted. However, due to recent safety concerns regarding the administration of L. rhamnosus strain GG and a lack of benefit in this interim analysis, the study was terminated by the study investigators.The results of this preliminary investigation were unexpected but important in view of the increased use of probiotic preparations in medically fragile pediatric patients. In this randomized, placebo-controlled trial, L. rhamnosus strain GG was not shown to be effective in reducing the incidence of nosocomial infections. In fact, a statistically nonsignificant trend toward an increase in infection was seen (four vs. 11). Further studies with a larger patient population are needed to establish both safety and efficacy of probiotics in pediatric critical care.

Introduction To describe ventilator management using a high-frequency percussive ventilator (HFPV), after other modes of mechanical ventilation failed. Design Case series. Setting Pediatric intensive care unit. Patients Previously healthy 11-month-old male with severe aspiration pneumonitis from mineral oil. Interventions The patient was initially placed on a conventional ventilator in a pressure-regulated volume-control mode but needed higher-than-normal pressures to maintain adequate ventilation. A decision was made to switch the patient to a pressure-control/pressure-support mode. At the end of the third day of pressure-control/pressure-support mode, a decision was made to attempt airway pressure-release ventilation. During a trial attempt, saturation levels deteriorated and a decision was made to place the patient on a high-frequency oscillator. The patient remained on this mode of ventilation for 6 days. On the sixth day, the chest radiograph showed a worsening of his pneumonia, and the patient started to deteriorate. A decision was made to try the HFPV in an attempt to mobilize secretions and any residual mineral oil. Immediately after initiating the HFPV and for 4 hrs thereafter, large amounts of secretions -- including a thick, oily substance -- were suctioned from the airways. Within 12-24 hrs, oxygenation improved dramatically and Fio2 was weaned. During the next 12 hrs, the patient was weaned off HFPV onto a conventional ventilator, and he was extubated 48 hrs after initiating HFPV. Conclusions In this case, HFPV used as an alternative mode of ventilation successfully mobilized secretions that were otherwise unobtainable and that we believe led to the swift recovery of this child. HFPV should be given consideration as a mode of ventilation when mobilization of secretions is an issue.

SUMMARY It is vital to the future intellectual health of cardiovascularmedicine and the welfare of pediatric patients with cardiovas-cular disease that all future pediatric cardiologists be familiarwith the principles and tools of research. Training in researchrequires the intense involvement of productive and establishedinvestigators. Those trainees preparing for a career in investi-gative cardiology require a carefully developed but flexibleeducational plan that will permit them to be successful in theirresearch careers over an extended period. REFERENCES 1. Sonnenblick EH, Ryan TI, Starke RD. Task force 7: training incardiovascular research. J Am Coll Cardiol 1995;25:25–8.2. Roberts R, Alexander RW, Loscalzo J, Williams RS. Task force 7:training in cardiovascular research. Available at: http://www.acc.org/clinical/training/cocats2.pdf 2002. Accessed August 10, 2004.3. NHLBI Task Force Report on Pediatric Cardiovascular Diseases.Available at: http://www.nhlbi.nih.gov/resources/docs/pediatric_cvd.pdf.Accessed August 10, 2004.

This paper examines National Institutes of Health (NIH) pediatric research spending in absolute terms and relative to the doubling of the NIH overall budget between fiscal years 1998 and 2003. Pediatric spending increased by an average annual rate of 12.8 percent during the doubling period (almost on par with the NIH average annual growth rate of 14.7 percent). However, the proportion of the total NIH budget devoted to the pediatric portfolio declined from 12.3 to 11.3 percent. We offer recommendations for implementing existing commitments to strengthen the pediatric research portfolio and to protect the gains of the doubling period.

The objective of this investigation was to compare how two modes of positive pressure ventilation affect cardiac output, airway pressures, oxygenation, and carbon dioxide removal in children with congenital heart disease in the immediate postoperative period. The investigation used a one group pretest–post-test study design and was performed in the pediatric cardiac intensive care unit in a university-affiliated children's hospital. Nine infants were enrolled immediately after repair of tetralogy of Fallot (2) or atrioventricular septal defects (7) with mean weight = 5.5 kg (4.2–7.3 kg). Children were admitted to the pediatric cardiothoracic intensive care unit after complete surgical repair of their cardiac defect and stabilized on a Siemen's Servo 300 ventilator in volume control mode (VCV1) (volume-targeted ventilation with a square flow wave pattern). Tidal volume was set at 15 cc/kg (total). Hemodynamic parameters, airway pressures and ventilator settings, and an arterial blood gas were measured. Patients were then changed to pressure-regulated volume control mode (PRVC) (volume-targeted ventilation with decelerating flow wave pattern) with the tidal volume set as before. Measurements were repeated after 30 minutes. Patients were then returned to volume control mode (VCV2) and final measurements made after 30 minutes. The measurements and results are as follows: After correction of congenital heart defects in infants, mechanical ventilation using a decelerating flow wave pattern resulted in a 19% decrease in peak inspiratory pressure without affecting hemodynamics, arterial oxygenation, or carbon dioxide removal.

The use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes.Retrospective, observational questionnaire study.Ten tertiary care pediatric intensive care units.Two hundred ninety patients managed with HFOV between January 1997 and June 1998.None.Patients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45.Given the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).

Objective: To determine the effects positive pressure ventilation have on left ventricular diastolic function in neonates after the arterial switch operation. Design: Prospective case series. Setting: Pediatric cardiac and multidisciplinary intensive care units in two university-affiliated children's hospitals. Patients and participants: The patient population consisted of 12 neonates weighing 2.5-4.2 kg with D-transposition of the great arteries (DTGA) who underwent arterial switch operation. Interventions: All patients were mechanically ventilated in a volume-targeted mode with a square wave flow pattern. The positive end-expiratory pressure was held constant. A long inspiratory time was set by extending it over three cardiac cycles. Measurements and results: Pulsed Doppler measurements of left ventricular diastolic function were performed during the following cardiac cycles: (1) the last diastolic period of expiration (E L ), (2) first, second and third diastolic periods of inspiration (I 1 , I 2 , I 3 ) and (3) the first diastolic period of expiration (E F ). Doppler measurements of peak E wave, peak A wave, E area/A area, E area fraction, A area fraction, 0.33 area fraction and the deceleration time were made. Doppler tracings were digitized and the data obtained from three sequential study periods were averaged. Data were statistically analyzed using the repeated measures analysis of variance procedure. During (I 1 ), there was a 21 % increase in the peak E wave (0.53 ± 0.06 vs 0.64 ± 0.08 m/s, p < 0.01) and 28 % increase in peak A wave (0.47 ± 0.07 vs 0.60 ± 0.08 m/s, p < 0.01) compared to (E L ). There was a 24 % increase in total area under the E and A waves when I 1 was compared to E L (0.059 ± 0.008 vs 0.073 ± 0.009, p < 0.01) and there was no change in mitral valve deceleration time. Compared to the initial diastolic period during inspiration (I 1 ), the third diastolic period during inspiration (I 3 ) had a 38 % decrease in peak E (0.64 ± 0.08 vs 0.40 ± 0.05 m/s, p < 0.01) and 33% decrease in peak A (0.60 ± 0.09 vs 0.40 ± 0.05 m/s, p < 0.01). In addition, there was a 16% reduction in total area under the E and A waves (0.073 ± 0.009 vs 0.061 ± 0.008, p < 0.01). There were no changes in the other diastolic indexes that reflect changes in ventricular compliance or relaxation. Conclusions: In neonates with transposition of the great arteries (TGA) after the arterial switch operation, positive pressure ventilation augments left ventricular filling during the early phase of inspiration. Prolonging the inspiratory time over three cardiac cycles results in a reduction in left ventricular filling during the third diastolic period. There were no changes in the other diastolic indexes that reflect changes in ventricular compliance or relaxation.

Kocis, Keith C., Peter J. Radell, Wayne I. Sternberger, Jane E. Benson, Richard J. Traystman, and David G. Nichols. Ultrasound evaluation of piglet diaphragm function before and after fatigue. J. Appl. Physiol. 83(5): 1654–1659, 1997.—Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial[Formula: see text] to 50–60 Torr (6.6–8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 ± 0.7 and 49 ± 11 cmH2O, respectively, and decreased to 6 ± 1.0 and 27 ± 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 ± 2 to 8 ± 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.

In summary, this data on baseline and follow-up Doppler flow characteristics of small caliber SJM prosthetic valves should be extremely valuable for identifying valve dysfunction in children. Because of the high risk of developing valve obstruction, these children should be closely monitored with serial Doppler examinations.