John F. Bealer

Plug the lung until it grows (PLUG): A new method to treat congenital diaphragmatic hernia in utero☆

Fetal lungs normally produce fluid that flows through the upper airway into the amniotic fluid. In fetuses with congenital diaphragmatic hernia (CDH), obstructing the flow of lung fluid may expand the lungs and propel the viscera from the chest, alleviating the pulmonary hypoplasia associated with CDH. To test this hypothesis, left-sided diaphragmatic hernias were created in sixteen 75-day-gestation fetal lambs (full-term, 145 days). At 120 days, the trachea was ligated in eight lambs; it was left unligated in the other eight. At 135 to 140 days, the fetuses were delivered, and a tracheostomy performed. Newborns were ventilated for 1 hour and then killed. Blood gas analysis was performed at 0,5,20,40, and 60 minutes. Lung dry weight, DNA, protein, and lipid analyses, as well as plasma cortisol measurements were performed. At autopsy, in the ligated lambs, the abdominal viscera was reduced from the thorax; however, the unligated lambs had viscera completely occupying the left chest. The lungs of the ligated lambs had a higher dry weight (4.22 +/- 1.37 g/kg v 1.95 +/- 0.59 g/kg; P =.001), DNA (193.8 +/- 90.5 mg/kg v 91.5 +/- 66.4 mg/kg; P = .02), and protein (1798 +/- 691.6 mg/kg v 766.6 +/- 201 mg/kg; P = .004). Lung saturated phosphatidyl choline (SPC) levels, DNA:protein ratio, and plasma cortisol were not different between the groups. Neonatal Po2 at 60 minutes was higher in the ligated group (179.4 +/- 127.0 mm Hg v 60.9 +/- 62.4 mm Hg; P < .05), and Pco2 was lower (44.1 +/- 21.4 v 83.9 +/- 23.5; P < .05) in the ligated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Operating on placental support: The ex utero intrapartum treatment procedure

While treating eight fetuses with predictable airway obstruction, the authors developed a systematic approach, the ex utero intrapartum treatment procedure, to secure the airway during delivery. Six patients had their trachea plugged or clipped in utero for treatment of congenital diaphragmatic hernia, and two patients had prenatally diagnosed cystic hygroma of the neck and oropharynx. The ex utero intrapartum treatment procedure was performed by using high doses of inhaled halogenated agents to facilitate uterine relaxation during cesarean section, securing the fetal airway while feto-placental circulation remained intact, and then dividing the umbilical cord. A variety of procedures were performed during the ex utero intrapartum treatment procedure including bronchoscopy, orotracheal intubation, tracheostomy, tracheostomy with retrograde orotracheal intubation, tracheoplasty, removal of internal tracheal plug, removal of external tracheal clip, central line placement, and instillation of surfactant. There were minimal maternal or fetal complications during the procedure. This approach requires the coordinated efforts of pediatric surgeons, obstetricians, anesthesiologists, sonographers, and neonatologists. The combination of intensive maternal-fetal monitoring, cesarean section with maximal uterine relaxation, and maintenance of intact feto-placental circulation provides a controlled environment for securing the airway in babies with prenatally diagnosed airway obstruction.

Shock after blast wave injury is caused by a vagally mediated reflex.

OBJECTIVE Bomb blast survivors occasionally suffer from profound shock and hypoxemia without signs of external injury. We hypothesize that a vagally mediated reflex such as the pulmonary defensive reflex is the cause of shock from blast wave injury. This study was a prospectively randomized, controlled animal study. METHODS By using a previously described model of blast wave injury, we randomized rats to one of four groups: control, blast-only, bilateral cervical vagotomy plus atropine 200 microg/kg i.p. only, and bilateral cervical vagotomy plus atropine 200 microg/kg i.p. before blast injury. Cardiopulmonary parameters were recorded for 90 minutes after the blast or until death. RESULTS Bradycardia, hypotension, and absence of compensatory peripheral vasoconstriction, typically seen in animals subjected to a blast pressure injury, were prevented by bilateral cervical vagotomy and intraperitoneal injection of atropine methyl-bromide. Hypoxia and lung injury were not statistically significant between the blasted groups, suggesting equivalent injury. CONCLUSION Our data implicate a vagally mediated reflex such as the pulmonary defensive reflex as the cause of shock seen immediately after a blast pressure wave injury.

Cardiopulmonary physiology of primary blast injury

OBJECTIVE Bomb blast survivors are occasionally found in profound shock and hypoxic without external signs of injury. We investigated the cardiovascular and pulmonary responses of rats subjected to a blast pressure wave. DESIGN Prospectively randomized, controlled animal study. MATERIALS AND METHODS Rats were instrumented and subjected to a blast pressure wave of different intensities from a blast wave generator. Cardiopulmonary parameters were recorded for 3 hours or until death. MEASUREMENTS AND MAIN RESULTS The cardiovascular response to a blast pressure wave was immediate bradycardia, hypotension, and low cardiac index. Three hours later, the rats developed hypotension, low cardiac index, and low stroke volume. Interestingly, systemic vascular resistance remained unchanged. The pulmonary response was a decreased PaO2 and stable PacO2, suggesting a ventilation-perfusion mismatch from massive pulmonary hemorrhage. CONCLUSIONS Blast-induced circulatory shock resulted from immediate myocardial depression without a compensatory vasoconstriction. Hypoxia presumably resulted from a ventilation-perfusion mismatch caused by pulmonary hemorrhage.

Experience with minimally invasive surgery in infants

BACKGROUND This study evaluates the feasibility, safety, and efficacy of performing advanced endoscopic procedures in infants under 5 kg. METHODS Over a 51-month period 183 infants weighing 1.3 to 5.0 kg underwent 195 procedures using minimally invasive techniques. The majority of the procedures were performed using 3.5-mm instruments and 2.7-mm scopes. Procedures include Nissen fundoplication, pyloromyotomy, colon pull-through, patent ductus arteriosus closure, Ladds procedure, colon resection, congenital diaphragmatic hernia repair, ovarian cyst excision, and exploration. RESULTS All but two procedures were completed successfully endoscopically. There were two intraoperative complications and no mortality. Days to discharge for patients admitted for their specific procedure were Nissen 2.1, patent ductus arteriosus 2, pyloromyotomy 1, and pull-through 3.4. CONCLUSIONS This study demonstrates that advanced endosurgical techniques in infants is safe, effective, and associated with the same benefit as that seen in older patients.

The incidence and spectrum of neurological injury after open fetal surgery

A preterm infants immature brain is susceptible to both anoxic and hemorrhagic injury during periods of physiological stress. The advent of in utero surgery has created a new population of premature patients at risk for central nervous system (CNS) injury. The aim of this study was to evaluate the frequency and nature of CNS injuries in fetal surgical patients. Of 33 fetuses with known neurological outcome after fetal surgery, CNS injuries were identified in seven (21%). Of the seven, four had significant episodes of fetal bradycardia (3) or neonatal hypotension (1), which suggests that asphyxia contributed to the neurological injury. The CNS injuries in the other three patients occurred unexpectedly and without associated signs of fetal distress. The authors speculate that these injuries may have been caused by sudden fluxes in cerebral blood flow, induced by maternal hypoxia (1) or by maternally administered tocolytic drugs (2) used to treat postoperative preterm labor.

Management of button battery-induced hemorrhage in children.

Objectives:Button battery ingestions are potentially life threatening for children. Catastrophic and fatal injuries can occur when the battery becomes lodged in the esophagus, where battery-induced injury can extend beyond the esophagus to the trachea or aorta. Increased production of larger, more powerful button batteries has coincided with more frequent reporting of fatal hemorrhage secondary to esophageal battery impaction, but no recommendations exist for the management of button battery–induced hemorrhage in children. Materials and Methods:We reviewed all of the reported pediatric fatalities due to button battery–associated hemorrhage. Our institution engaged subspecialists from a wide range of disciplines to develop an institutional plan for the management of complicated button battery ingestions. Results:Ten fatal cases of button battery–associated hemorrhage were identified. Seven of the 10 cases have occurred since 2004. Seventy percent of cases presented with a sentinel bleeding event. Fatal hemorrhage can occur up to 18 days after endoscopic removal of the battery. Guidelines for the management of button battery–associated hemorrhage were developed. Conclusions:Pediatric care facilities must be prepared to act quickly and concertedly in the case of button battery–associated esophageal hemorrhage, which is most likely to present as a “sentinel bleed” in a toddler.

S100A8/A9: A Potential New Diagnostic Aid for Acute Appendicitis

OBJECTIVES Diagnosing acute appendicitis is a daunting clinical challenge, as there is no single test that reliably distinguishes acute appendicitis from other etiologies of acute abdominal pain. In this study, the authors examined whether circulating levels of S100A8/A9 could be useful as a marker to aid in the diagnosis of acute appendicitis. METHODS Plasma samples from emergency department (ED) patients with acute abdominal pain (n=181) were tested using an immunoassay for S100A8/A9. RESULTS The sensitivity and specificity for S100A8/A9 in diagnosing acute appendicitis were estimated to be 93% (95% confidence interval [CI]=81% to 97%) and 54% (95% CI=45% to 62%), respectively. Negative predictive value (NPV) was 96% (95% CI=89% to 99%), and positive predictive value (PPV) was 37% (95% CI=28% to 47%). Performance characteristics of elevated white blood cell (WBC) count were also estimated: sensitivity 63% (95% CI=47% to 76%), specificity 67% (95% CI=59% to 75%), NPV 86% (95% CI=78% to 91%), and PPV 36% (95% CI=26% to 47%). CONCLUSIONS This is the first report exploring the relationship between circulating S100A8/A9 and acute appendicitis and establishes proof of concept for this biomarker as a diagnostic test for acute appendicitis. Further studies are indicated to optimize the use of this biomarker, in conjunction with other established approaches.

Gastroschisis increases small bowel nitric oxide synthase activity

In gastroschisis, the eviscerated fetal bowel frequently is damaged and this results in hypoperistalsis and malabsorption. The mechanistic link that ties gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO) and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit model, the authors investigated the hypothesis that the hypoperistalsis and malabsorption associated with gastroschisis may be attributable to abnormal small bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion assay, they measured NO synthase activity in the small bowel of full-term fetal rabbits with and without gastroschisis. The mean total small bowel NO synthase activity of fetal rabbits with gastroschisis was 2.5 times greater than that of control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537 mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was studied by measuring the individual isoforms of NO synthase, and the site of increased NO synthase activity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO synthase activity, the authors explored the mechanism of this increase using NADPH-diaphorase staining. With this histological staining technique, no quantitative increase was found in the small bowel NO synthase of the rabbits with gastroschisis. This suggests that the increased NO synthase activity found in these rabbits is the result of accelerated enzyme kinetics. These findings suggest that the increased NO synthase activity caused by gastroschisis may contribute to the common clinical sequelae of malabsorption and intestinal dysmotility.

Treating the snakebitten child in North America: A study of pit viper bites

BACKGROUND/PURPOSE Snakebite envenomation is a potentially life-threatening form of trauma, the dangers of which are amplified in children because their smaller size increases the relative dose of venom received. The authors reviewed a large series of snakebitten children to address the medical and fiscal issues of treating these patients. METHODS The records of 37 snakebitten children (1987 through 1997) were analyzed for demographic data, signs of envenomation, use of specific therapies (antivenin, blood products, or surgery), length of hospitalization, complications, and cost of care. RESULTS Fifty-four percent of the children had a major envenomation demonstrated by systemic symptomatology, laboratory analysis, or need for surgery. All children made full recoveries with most receiving only supportive care (92%). The average time to emergency department presentation was 8 hours, where all children with major envenomations and those requiring specific therapies (surgery, clotting factors) were identified. Cost analysis showed an average of